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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.

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.

Ask a specific question about this device

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)
• 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, V. vulnificus, 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 pouch to drive 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.

The provided document is a 510(k) premarket notification for the BIOFIRE FILMARRAY Gastrointestinal (GI) Panel. The purpose of this submission is to update the device's instructions for use with additional clinical data, specifically regarding the Norovirus GI/GII assay.

Here's an analysis based on your requested information:

1. Table of Acceptance Criteria and Reported Device Performance

The acceptance criteria are implied by the clinical performance results presented, particularly for Norovirus GI/GII, as the reason for this submission is to update the labeling based on a post-market performance follow-up (PMPF) study that yielded different results from the original clinical study. The document does not explicitly state pre-defined acceptance criteria for the PMPF study to be deemed acceptable. However, the reported performance is provided.

Note: The document focuses on updating the instructions for use due to a detected change in Norovirus GI/GII assay performance compared to original labeling claims, rather than defining new acceptance criteria for the device as a whole.

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

• Test Set Sample Size: 872 clinical specimens.
• Data Provenance: Prospective clinical evaluation conducted from April through July 2023. The country of origin is not explicitly stated, but the submission is to the U.S. FDA, suggesting the study was likely conducted in the United States or followed U.S. regulatory guidelines.

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

This information is not provided in the document. The document refers to a "more recent version of the US CDC Norovirus assay" used for comparison, implying it was used as a reference method for ground truth, but does not detail the process of establishing ground truth for the clinical specimens or the role of experts in that process.

4. Adjudication Method for the Test Set

This information is not provided in the document.

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

No, an MRMC comparative effectiveness study was not done. This device is an in vitro diagnostic (IVD) test for nucleic acid detection, not an AI-assisted diagnostic device for human readers. Therefore, the concept of human readers improving with AI assistance is not applicable.

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

Yes, the performance data presented is for the standalone (algorithm only) performance of the BIOFIRE GI Panel. The device is an automated multiplex nucleic acid-based assay; its results are generated directly by the system without human interpretation of raw data, which is then reported.

7. The Type of Ground Truth Used

The ground truth for the Norovirus GI/GII assay in the PMPF study was established by comparison to a "more recent version of the US CDC Norovirus assay." For one false negative (FN) specimen, "bi-directional sequencing analysis" was used to detect Norovirus. For 3 out of 29 false positive (FP) specimens, "bi-directional sequencing analysis" also detected Norovirus. For the remaining false positives, cross-reactivity was identified through analytical testing and in silico analysis. This indicates a combination of:

• Reference laboratory method (US CDC Norovirus assay): This serves as the primary comparative method.
• Sequencing (Bi-directional sequencing analysis): Used for discrepancy resolution and further investigation of false positive/negative results.
• Analytical testing and In silico analysis: Used to confirm and identify cross-reactive organisms.

8. The Sample Size for the Training Set

This information is not provided in the document. The document focuses on the clinical evaluation data used to update the device's labeling, not data related to the original development or training of the assay.

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

This information is not provided in the document. As this submission is for an update based on a post-market study, details about the original training set and its ground truth establishment are not included.

Ask a specific question about this device

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.

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.

Ask a specific question about this device

The FilmArray Gastrointestinal (GI) Panel is a qualitative multiplexed in vitro diagnostic test intended for use with FilmArray systems. The FilmArray 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 FilmArray GI Panel:

• · Campylobacter (C. jejuni/C. coli/C. upsaliensis)
• · Clostridium difficile (C. difficile) toxin A/B
• Plesiomonas shigelloides
• · Salmonella
• · Vibrio (V. parahaemolyticus/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 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 FilmArray 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 FilmArray 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, V. vulnificus, and Vibrio cholerae) were established primarily using contrived clinical specimens.

Negative FilmArray 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.

The FilmArray Gastrointestinal (GI) Panel is a multiplex nucleic acid test designed to be used with FilmArray systems. The FilmArray GI pouch contains freeze-dried reagents to perform nucleic acid purification and nested, multiplex PCR with DNA melt analysis. The FilmArray Gastrointestinal (GI) Panel simultaneously conducts 22 tests for the identification of GI pathogens from stool specimens collected in Cary Blair transport medium (Table 1). Results from the FilmArray GI Panel test are available within about one hour.

A test is initiated by loading Hydration Solution into one port of the FilmArray pouch and a stool sample (in Cary Blair transport medium) mixed with the provided Sample Buffer into the other port of the FilmArray GI pouch and placing it in the FilmArray Instrument. The pouch contains all of the reagents required for specimen testing and analysis in a freeze-dried format; the addition of Hydration Solution and sample/Sample Buffer Mix rehydrates the reagents. After the pouch is prepared, the FilmArray Software guides the user though the steps of placing the pouch into the instrument, scanning the pouch barcode, entering the sample identification, and initiating the run.

The FilmArray instrument 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. 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 pouch to drive the PCR reactions and the melt curve analysis.

Nucleic acid extraction occurs within the FilmArray pouch using mechanical and chemical lysis followed by purification using standard magnetic bead technology. After extracting and purifying nucleic acids from the unprocessed sample, a nested multiplex PCR is executed in two stages. During the first stage, a single, large volume, highly multiplexed reverse transcription PCR (rt-PCR) reaction is performed. 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 Defense, LLC). 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 each well of the array. At the conclusion of the 240 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 array captures fluorescent images of the PCR2 reactions and software interprets the data.

The FilmArray 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 provided text describes the FilmArray Gastrointestinal (GI) Panel, a qualitative multiplexed in vitro diagnostic test for the simultaneous detection and identification of nucleic acids from multiple bacteria, viruses, and parasites directly from stool samples. The document focuses on demonstrating substantial equivalence of the FilmArray GI Panel for use with the FilmArray 2.0 system to a previously cleared FilmArray GI Panel (K140407) used with the original FilmArray system.

The acceptance criteria are not explicitly stated as clear thresholds in the provided document. However, the study aims to demonstrate concordance and reproducibility between the modified system (FilmArray 2.0) and the current (predicate) system for all listed analytes, indicating that performance should be comparable to or better than the predicate device.

The reported device performance (FilmArray GI Panel for use with FilmArray 2.0) is detailed in two main studies: Clinical Performance and Reproducibility, comparing it against the original FilmArray system.

1. Table of Acceptance Criteria and Reported Device Performance

Since explicit acceptance criteria are not provided, I will derive implied criteria from the study results and present the reported performance against these implied criteria.

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The FilmArray Gastrointestinal (GI) Panel is a qualitative multiplexed nucleic acid-based in vitro diagnostic test intended for use with the FilmArray Instrument. The FilmArray 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 FilmArray GI Panel:

• Campylobacter (C. jejuni/C. coli/C. upsaliensis) .
• 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) It/st .
• Shiga-like toxin-producing Escherichia coli (STEC) stx1/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 FilmArray 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 FilmArray 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 O157, Plesiomonas shigelloides, Yersinia enterocolitica, Astrovirus, and Rotavirus A were established primarily with retrospective clinical specimens.

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

Negative FilmArray Gl 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 noninfectious 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.

The FilmArray Gastrointestinal (GI) Panel is a multiplex nucleic acid test designed to be used with the FilmArray Instrument. The FilmArray GI pouch contains freeze-dried reagents to perform nucleic acid purification and nested, multiplex PCR with DNA melt analysis. The FilmArray Gastrointestinal (GI) Panel simultaneously conducts 22 tests for the identification of GI pathogens from stool specimens collected in Cary Blair transport medium (Table 1). Results from the FilmArray GI Panel test are available within about one hour.

A test is initiated by loading Hydration Solution into one port of the FilmArray pouch and a stool sample (in Cary Blair transport medium) mixed with the provided Sample Buffer into the other port of the FilmArray GI pouch and placing it in the FilmArray Instrument. The pouch contains all of 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 FilmArray Software guides the user though the steps of placing the pouch into the instrument, scanning the pouch barcode, entering the sample identification, and initiating the run.

The FilmArray Instrument 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 pouch to drive the PCR reactions and the melt curve analysis.

Nucleic acid extraction occurs within the FilmArray pouch using mechanical and chemical Ivsis followed by purification using standard magnetic bead technology. After extracting and purifying nucleic acids from the unprocessed sample, the FilmArray performs a nested multiplex PCR that is executed in two stages. During the first stage, the FilmArray 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®, BioFire). 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 singleplex fashion in each well of the array. At the conclusion of the 2nd stage PCR, the arrav 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 200 stage PCR captures fluorescent images of the PCR reactions and software interprets the data.

The FilmArray 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 FilmArray Gastrointestinal (GI) Panel is a qualitative multiplexed nucleic acid-based in vitro diagnostic test for 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.

1. Table of Acceptance Criteria and Reported Device Performance:

The document lists "Positive Percent Agreement (PPA)" and "Negative Percent Agreement (NPA)" as performance measures, which can be interpreted as sensitivity and specificity. While acceptance criteria are not explicitly stated as numerical thresholds for PPA and NPA, a general expectation for diagnostic assays is high agreement with the reference method. The reported performance varies by analyte. For the purpose of this output, the reported device performance for selected analytes is presented below. A comprehensive table for all analytes can be found in Table 6 of the provided document.

2. Sample size used for the test set and the data provenance:

• Prospective Clinical Study:
  • Sample Size: 1556 residual stool specimens. Originally 1578 were acquired, but 22 were excluded.
  • Data Provenance: The study was multi-center, conducted at four geographically distinct U.S. study sites (Pacific, North Central, Great Lakes, and Northeast regions). The data is prospective.
• Archived Specimens:
  • Sample Size: 222 preselected archived clinical specimens.
  • Data Provenance: Retrospective, as these were archived specimens. Countries of origin are not specified beyond being "clinical specimens."
• Contrived Specimens:
  • Sample Size: Varies by analyte, but generally tested using at least 50 spiked specimens for each organism or 75 unspiked specimens. For example, for Entamoeba histolytica, 50 positive and 75 negative contrived specimens were used.
  • Data Provenance: Created in the laboratory using residual negative specimens from the prospective clinical study, spiked with known organisms.

3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts:

The document does not specify the number of experts used or their qualifications for establishing the ground truth. It refers to "appropriate comparator/reference methods," which include "standard manual and automated microbiological/biochemical identification methods" for bacteria and "PCR with Bi-directional Sequencing" for other pathogens. These methods likely rely on trained laboratory personnel, but no explicit mention of "experts" and their qualifications (e.g., "radiologist with 10 years of experience") is made in the context of ground truth establishment for the clinical performance study.

4. Adjudication method (e.g., 2+1, 3+1, none) for the test set:

The document describes a discrepancy resolution process. For the clinical study, if the FilmArray GI Panel result differed from the initial reference/comparator method, bi-directional sequence analysis was performed. Specifically, for discrepant results in mixed infections (where the FilmArray detected organisms not found by reference methods), bi-directional sequence analysis was used to confirm the presence of the analyte. This suggests an adjudication method based on a higher-tier molecular technique (sequencing) for discordant results. However, a formal "X+Y" adjudication method where multiple initial readers are involved is not described.

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:

This is an in vitro diagnostic device (nucleic acid-based assay), not an AI-powered diagnostic imaging device or an assay with a human "reader" component that would involve interpretation (like a radiologist reading an image). Therefore, a multi-reader multi-case (MRMC) comparative effectiveness study involving human readers and AI assistance is not applicable and was not performed. The device provides an automated "Detected" or "Not Detected" result.

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

Yes, the clinical evaluation presented is a standalone performance study. The FilmArray GI Panel is an automated nucleic acid test that provides results directly. The software automatically interprets the results and provides a test result for each organism on the panel (Page 3). There is no human-in-the-loop component for result interpretation for the primary output of the device.

7. The type of ground truth used (expert consensus, pathology, outcomes data, etc.):

The ground truth was established using a combination of:

• Bacterial Culture with Microbiological/Biochemical Identification: For most bacterial targets (e.g., Campylobacter, E. coli O157, Plesiomonas shigelloides, Salmonella, Vibrio, Yersinia enterocolitica, STEC, ETEC, EPEC, EIEC/Shigella, EAEC).
• PCR with Bi-directional Sequencing: For viruses and parasites, and for confirming discrepant bacterial results from culture (e.g., for Norovirus, Sapovirus, Cryptosporidium, Giardia lamblia). Bi-directional sequencing was also used to identify species within bacterial groups when standard methods couldn't.

8. The sample size for the training set:

The document does not explicitly mention a "training set" in the context of machine learning or algorithm development for interpretation. This is a molecular diagnostic assay, and its performance is based on the specificity of its primers and probes and the robustness of the PCR and melt curve analysis. The development process would involve extensive optimization and testing of these components. However, the document does describe analytical studies such as Limit of Detection (LoD) and Inclusivity/Exclusivity tests, which involve testing a large number of isolates and contrived samples to define the operational characteristics of the assay. For instance, the inclusivity study evaluated 270 isolates representing the diversity of FilmArray GI Panel analytes.

9. How the ground truth for the training set was established:

As noted above, a traditional "training set" in the machine learning sense is not described. However, the "ground truth" for the analytical studies (Limit of Detection, Inclusivity, Exclusivity) was established by:

• Quantified organism preparations: For LoD studies, organisms were spiked at known concentrations into negative sample matrix.
• Well-characterized isolates/strains: For inclusivity, a collection of 270 isolates representing the diversity of relevant species/serotypes was used. Their identity would have been confirmed by standard microbiological and molecular methods.
• Bioinformatics/in silico analysis: For organisms not empirically tested, in silico analysis of sequence data was used to predict reactivity against the assay primers, effectively serving as a computational "ground truth."

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