Search Results

The BIOFIRE SPOTFIRE Respiratory/Sore Throat (R/ST) Panel Mini is an automated multiplexed polymerase chain reaction (PCR) test intended for use with the BIOFIRE SPOTFIRE System for the simultaneous, qualitative detection and identification of multiple respiratory viral and bacterial nucleic acids in nasopharyngeal swab (NPS) or anterior nasal swab (ANS) specimens obtained from individuals with signs and symptoms of respiratory tract infection, including COVID-19; (Respiratory menu) or in throat swab (TS) specimens from individuals with signs and symptoms of pharyngitis; (Sore Throat menu).

The following analytes are identified and differentiated using the BIOFIRE SPOTFIRE R/ST Panel Mini:

Respiratory Menu
Viruses

• Coronavirus SARS-CoV-2
• Human rhinovirus
• Influenza A virus
• Influenza B virus
• Respiratory syncytial virus

Sore Throat Menu
Viruses

• Human rhinovirus
• Influenza A virus
• Influenza B virus
• Respiratory syncytial virus

Bacteria

• Streptococcus pyogenes (group A Strep)

Nucleic acids from the viral and bacterial organisms identified by this test are generally detectable in NPS/ANS/TS specimens during the acute phase of infection. The detection and identification of specific viral and bacterial nucleic acids from individuals exhibiting signs and symptoms of respiratory infection and/or pharyngitis is indicative of the presence of the identified microorganism and aids in diagnosis if used in conjunction with other clinical and epidemiological information, and laboratory findings. The results of this test should not be used as the sole basis for diagnosis, treatment, or other patient management decisions.

Negative results in the setting of a respiratory illness and/or pharyngitis may be due to infection with pathogens that are not detected by this test, or a respiratory tract infection that may not be detected by an NPS, ANS, or TS specimen. Positive results do not rule out co-infection with other organisms. The agent(s) detected by the BIOFIRE SPOTFIRE R/ST Panel Mini may not be the definite cause of disease.

Additional laboratory testing (e.g., bacterial and viral culture, immunofluorescence, and radiography) may be necessary when evaluating a patient with possible respiratory tract infection and/or pharyngitis.

The BIOFIRE SPOTFIRE R/ST Panel Mini (SPOTFIRE R/ST Panel Mini) simultaneously identifies 5 different respiratory viral pathogens in nasopharyngeal swabs (NPS) or anterior nasal swabs (ANS), or 5 different viral and bacterial pharyngitis pathogens in throat swabs (TS) from individuals with signs and symptoms of respiratory tract infections or pharyngitis, respectively, (see Table 1). The SPOTFIRE R/ST Panel Mini is compatible with the BIOFIRE® SPOTFIRE® System, a polymerase chain reaction (PCR)-based in vitro diagnostic system for infectious disease testing. The BIOFIRE SPOTFIRE System Software executes the SPOTFIRE R/ST Panel Mini test and interprets and reports the test results. The SPOTFIRE R/ST Panel Mini was designed to be used in CLIA-waived environments.

A test is initiated by loading Hydration Solution into the hydration solution injection port of the SPOTFIRE R/ST Panel Mini pouch and NPS, ANS, or TS specimen, mixed with the provided Sample Buffer, into the other sample injection port of the SPOTFIRE R/ST Panel Mini pouch and placing it in the SPOTFIRE 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 SPOTFIRE System Software guides the user through the steps of placing the pouch into the instrument, scanning the pouch barcode, entering the sample identification, and initiating the run.

Nucleic acid extraction occurs within the SPOTFIRE R/ST Panel Mini 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 SPOTFIRE System performs a nested multiplex PCR that is executed in two stages. During the first stage, the SPOTFIRE 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 singleplex fashion in each well of the array. At the conclusion 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 SPOTFIRE System 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 SPOTFIRE R/ST Panel Mini.

The FDA 510(k) clearance letter details the acceptance criteria and study that proves the BIOFIRE SPOTFIRE Respiratory/Sore Throat Panel Mini meets these criteria, specifically for the addition of Anterior Nasal Swabs (ANS) as a sample type for the Respiratory Menu.

Here's the breakdown:

1. Table of Acceptance Criteria and Reported Device Performance

The acceptance criteria are implicitly defined by the reported performance metrics (Positive Percent Agreement - PPA and Negative Percent Agreement - NPA) in the clinical study. The device is deemed to meet these criteria if the lower bound of the 95% Confidence Interval (95% CI) for PPA and NPA is above acceptable thresholds (though specific numerical thresholds for "acceptable" are not explicitly stated as separate criteria, the observed high performance and clearance imply they were met).

Archived Specimen Performance for Influenza B virus:

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

• Test Set Sample Size:
  • Clinical Performance (Prospective Study): 797 specimens (out of 820 initially enrolled, 23 excluded).
  • Archived Specimen Testing: 241 specimens for Influenza B virus (35 positive, 206 negative).
• Data Provenance:
  • Country of Origin: US (prospective multi-center study at five geographically distinct urgent care or emergency department study sites).
  • Retrospective/Prospective: The study was primarily prospective, conducted from March 2024 to February 2025. This was supplemented with archived specimens for Influenza B due to low prevalence in the prospective study.

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

The document does not explicitly state the number or qualifications of experts used to establish the ground truth. It states that the performance was evaluated by comparing the test results with those from a "commercially available FDA-cleared multiplexed respiratory pathogen panel." This suggests that the ground truth was established by the results of this comparator method, which themselves would have been validated. No human expert interpretation of the comparator method is described.

4. Adjudication Method for the Test Set

The document mentions "Investigations of discrepant results are summarized in the footnotes." These footnotes indicate that for discrepant cases (e.g., false positives, false negatives), "additional molecular methods" were used to re-test the specimens. This implies a form of post-hoc adjudication using a more definitive or orthogonal molecular method to resolve discrepancies between the SPOTFIRE R/ST Panel Mini and the initial comparator.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done

No. This study is for a diagnostic PCR test, not an AI-assisted imaging or interpretation device. Therefore, an MRMC study and analysis of human reader improvement with AI assistance are not applicable.

6. If a Standalone (i.e., Algorithm Only Without Human-in-the-Loop Performance) Was Done

Yes. The study evaluates the performance of the BIOFIRE SPOTFIRE R/ST Panel Mini as a standalone diagnostic device. The results are automatically interpreted and reported by the system software, with no human interpretation step in the primary analysis flow. The study compares the device's output directly to the comparator method.

7. The Type of Ground Truth Used

The primary ground truth was established by a commercially available FDA-cleared multiplexed respiratory pathogen panel. For discrepant results, "additional molecular methods" were used for confirmatory testing, indicating a molecular gold standard approach.

8. The Sample Size for the Training Set

The document does not provide details about a training set size. This notice is a 510(k) clearance for a PCR-based in vitro diagnostic test, not a machine learning or AI algorithm in the traditional sense that requires distinct training and test sets in the same manner. The "test set" described is the clinical validation cohort for demonstrating performance. PCR assays are generally developed and optimized through laboratory analytical studies, not typically "trained" on large datasets in the way an AI model would be.

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

As noted above, the concept of a "training set ground truth" is not applicable in this context, as the device is a PCR assay. The development and optimization of such assays involve different molecular and analytical validation processes to ensure specificity and sensitivity.

Ask a specific question about this device

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 Blood Culture Identification 2 (BCID2) Panel is a multiplexed nucleic acid test intended for use with BIOFIRE FILMARRAY 2.0 or BIOFIRE FILMARRAY TORCH Systems for the simultaneous qualitative detection and identification of multiple bacterial and yeast nucleic acids and select genetic determinants associated with antimicrobial resistance. The BIOFIRE BCID2 Panel test is performed directly on blood culture samples identified as positive by a continuous monitoring blood culture system. Results are intended to be interpreted in conjunction with Gram stain results. The following organism types and subtypes are identified using the BIOFIRE BCID2 Panel: Gram Positive Bacteria Enterococcus faecalis Staphylococcus spp. Streptococcus spp. Enterococcus faecium Staphylococcus aureus Streptococcus agalactiae (Group B) Listeria monocytogenes Staphylococcus epidermidis Streptococcus pneumoniae Staphylococcus lugdunensis Streptococcus pyogenes (Group A) Gram Negative Bacteria Acinetobacter calcoaceticus-baumannii complex Enterobacterales Bacteroides fragilis Enterobacter cloacae complex Haemophilus influenzae Escherichia coli Neisseria meningitidis (encapsulated) Klebsiella aerogenes Pseudomonas aeruginosa Klebsiella oxytoca Stenotrophomonas maltophilia Klebsiella pneumoniae group Proteus spp. Salmonella spp. Serratia marcescens Yeast Candida albicans Candida krusei Cryptococcus neoformans/gattii Candida auris Candida parapsilosis Candida glabrata Candida tropicalis The BIOFIRE BCID2 Panel contains assays for the detection of genetic determinants associated with resistance to methicillin (mecA/C and mecA/C in conjunction with MREJ, vancomycin (vanA and vanB), ß-lactams including penicillins, cephalosporins, monobactams, and carbapenems (blaCTX-M, blaIMP, blaKPC, blaNDM, blaOXA48-like, blaVIM) to aid in the identification of potentially antimicrobial-resistant organisms in positive blood culture samples. In addition, the panel includes an assay for the mobilized genetic determinant mor-1, an emerging marker of public health importance. The antimicrobial resistance gene or may not be associated with the agent responsible for disease. Negative results for these select antimicrobial resistance gene and marker assays do not indicate susceptibility, as multiple mechanisms of resistance to methicillin, vancomycin, b-lactams, and colistin exist. Antimicrobial Resistance Genes CTX-M KPC mecA/C NDM vanA/B IMP mcr-1 mecA/C and MREJ (MRSA) OXA-48-like VIM The BIOFIRE BCID2 Panel is indicated as an aid in the diagnosis of bloodstream infection and results should be used in conjunction with other clinical and laboratory findings. Positive results do not rule out co-infection with organisms not included in the BIOFIRE BCID2 Panel. The BIOFIRE BCID2 Panel is not intended to monitor treatment for bloodstream infection. Subculturing of positive blood cultures is necessary to recover organisms for susceptibility testing and epidemiological typing, to identify organisms in the blood culture that are not detected by the BIOFIRE BCID2 Panel, and for determination of species detected but not identified within complexes, groups, or genera by the BIOFIRE BCID2 Panel assays.

The BIOFIRE Blood Culture Identification 2 (BCID2) Panel is designed to simultaneously identify 43 bacteria and yeast responsible for bloodstream infections, as well as select genetic determinants of antimicrobial resistance (see Table 1), in a timeframe (about an hour) that allows the test results to be used in determining appropriate patient treatment and management. The BIOFIRE BCID2 Panel is performed directly on positive blood culture samples. The BIOFIRE BCID2 Panel is compatible with BioFire's PCR-based in vitro diagnostic BIOFIRE FILMARRAY 2.0 and FILMARRAY TORCH systems for infectious disease testing. A specific software module (i.e., BIOFIRE BCID2 Panel pouch module) is used to perform BIOFIRE BCID2 Panel testing on these systems. A test is initiated by loading Hydration Solution into one port of the BIOFIRE pouch and positive blood culture specimen mixed with the provided Sample Buffer into the other port of the BIOFIRE BCID2 Panel 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 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 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.

Here's a breakdown of the acceptance criteria and the study information based on the provided FDA 510(k) summary for the BioFire Blood Culture Identification 2 (BCID2) Panel:

1. Table of Acceptance Criteria and Reported Device Performance:

The document primarily focuses on a software update to mitigate a risk of false negative results for C. tropicalis specifically. It states that the re-analysis with the modified software led to a "very minor adjustment to clinical sensitivity for S. epidermidis from 96.5% [93.0-98.2%] to 96.9%".

The summary does not provide a comprehensive table of acceptance criteria and the overall device performance for all targets. Instead, it highlights the impact of the software update on C. tropicalis detection and the resulting minor change in S. epidermidis sensitivity.

Acceptance Criteria (Implied / Pre-established for Original Device):

While not explicitly stated as "acceptance criteria" in this specific document, the overall context of a 510(k) clearance implies that the device must demonstrate comparable performance to its predicate. The key focus of this Special 510(k) is to show that the software update does not adversely affect, and in fact, improves, the device's performance, particularly concerning the false negative C. tropicalis issue. The acceptance criterion for this update seems to be that the corrected software resolves the C. tropicalis issue and does not significantly degrade performance on other targets.

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

• Test Set Sample Size: The document refers to "reanalysis of the performance data (clinical and non-clinical studies) with the modified pouch module software." It explicitly mentions that the C. tropicalis issue was identified during testing of Maine Molecular Quality Controls, Inc. (MMQC) FilmArray BCID2 Control Panel M416. While the specific number of tests performed on this control or other test sets with the modified software is not given in this summary, the "reanalysis of the performance data" implies that the original clinical and non-clinical study data from the predicate device (K193519) was re-evaluated using the new software.
• Data Provenance: The issue was identified through testing with an external control material (C. tropicalis synthetic control material). The "reanalysis of the performance data (clinical and non-clinical studies)" implies that data from the original (K193519) approval was used, which would have primarily involved prospective clinical samples from various geographic locations. However, this specific document does not detail the provenance of the original clinical data. The new data generated to address the C. tropicalis issue was from synthetic control material.

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

• This information is not provided in the given FDA summary. The document focuses on a software update to an already cleared device, addressing a technical issue related to melting temperature analysis. The ground truth for the original clinical studies would have been established through a combination of clinical methods (e.g., standard microbiological culture and identification, susceptibility testing), but those details are not part of this specific Special 510(k) summary.

4. Adjudication Method for the Test Set:

• This information is not provided in the given FDA summary. For the original clinical studies related to the predicate device, an adjudication method (e.g., expert panel review of discrepancies) would likely have been employed, but this specific document does not detail it.

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 not applicable. The device (BIOFIRE Blood Culture Identification 2 Panel) is a fully automated multiplex nucleic acid test. It does not involve human readers interpreting results in the same way an imaging AI device would. Therefore, an MRMC study with human readers and AI assistance is not relevant to this device.

6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done:

• Yes. The BIOFIRE BCID2 Panel operates as a standalone diagnostic system. The "pouch module software" automatically interprets the melt curve analysis and combines data with internal controls to generate a test result. The description explicitly states, "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." There is no "human-in-the-loop" performance component for result generation, although clinical interpretation of results in conjunction with Gram stain and other findings is required.

7. The Type of Ground Truth Used (expert consensus, pathology, outcomes data, etc.):

• For the specific issue addressed in this Special 510(k) regarding C. tropicalis, the ground truth was known composition of synthetic control material.
• For the broader re-analysis of "clinical and non-clinical studies" (referring to the original predicate data), the ground truth for microbial identification in blood cultures typically involves standard microbiological culture (subculturing) and definitive identification methods (e.g., biochemical tests, mass spectrometry, sequencing), often supplemented by clinical context. The document emphasizes that "Subculturing of positive blood cultures is necessary to recover organisms for susceptibility testing and epidemiological typing, to identify organisms in the blood culture that are not detected by the BIOFIRE BCID2 Panel, and for determination of species detected but not identified within complexes, groups, or genera by the BIOFIRE BCID2 Panel assays," highlighting the role of traditional microbiology as a gold standard.

8. The Sample Size for the Training Set:

• This information is not provided in the given FDA summary, as the nature of this submission is a software update to an existing device, not a de novo algorithm development. The "pouch module software" utilizes pre-defined melting temperature (Tm) ranges and analysis parameters. The "reanalysis to include data generated from synthetic control materials" effectively served to refine or "retrain" specific parameters (Tm ranges) within the existing analytical framework, but the original training set size for the entire panel's algorithm is not detailed here.

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

• This information is not provided in the given FDA summary. For the original development of the BIOFIRE BCID2 Panel, the ground truth for establishing the algorithms' detection parameters and Tm ranges would have been based on extensive analytical studies using well-characterized microbial isolates (strains with confirmed identities) at various concentrations, likely identified by definitive culture-based methods and sequencing. The update specifically states that "Data from the synthetic control material(s) had not been included in the establishment and validation of the assay Tm ranges used for analysis by the pouch module software," indicating that the "training" for the C. tropicalis Tm range was incomplete previously and was corrected by incorporating this synthetic control material data.

Ask a specific question about this device

The BIOFIRE FILMARRA Y Tropical Fever (TF) Panel is an automated qualitative, multiplexed, polymerase chain reaction (PCR) test intended for use with BIOFIRE FILMARRAY 2.0 and BIOFIRE FILMARRAY TORCH Systems. The BIOFIRE FILMARRAY TF Panel detects and identifies selected bacterial, viral, and parasitic nucleic acids directly from EDTA whole blood collected from individuals with signs and/or symptoms of acute febrile illness or recent acute febrile illness and known or suspected exposure to the following target pathogens: chikungunya virus, dengue virus (serotypes 1, 2, 3 and 4), Leptospira spp., and Plasmodium species differentiation of Plasmodium falciparum and Plasmodium vivax/ovale).

Evaluation for more common causes of acute febrile illness (e.g., infections of the upper and lower respiratory tract or gastroenteritis, as well as non-infectious causes) should be considered prior to evaluation with this panel. Results are meant to be used in conjunction with other clinical, epidemiologic, and laboratory data, in accordance with the guidelines provided by the relevant public health authorities.

The BIOFIRE FILMARRA Y TF Panel is not intended to be used as the sole basis for diagnosis, treatment, or other management decisions. Positive results do not rule out co-infection with other organisms not included on the BIOFIRE FILMARRA Y TF Panel, nor do negative results rule out infection. Negative results from the BIOFIRE FILMARRA Y TF Panel may require additional testing if clinically indicated. Not all pathogens that cause acute febrile illness are detected by this test, and negative results do not rule out the presence of other infections.

In the United States, patient travel history, exposure risk, and consultation of the CDC Yellow Book should be considered prior to use of the BIOFIRE FILMARRAY TF Panel as some pathogens are more common in certain geographical locations.

The BIOFIRE FILMARRAY TF Panel is a rebranded version of the BioFire Global Fever Panel. It is designed to simultaneously identify 6 pathogens from whole blood specimens collected in EDTA tubes. The BIOFIRE FILMARRAY TF Panel is compatible with BioFire's PCR-based in vitro diaqnostic BIOFIRE® FILMARRAY® 2.0 and BIOFIRE® FILMARRAY® TORCH Systems for infectious disease testing. A panel-specific software module (i.e., BIOFIRE FILMARRAY TF Panel pouch module software) is used to perform BIOFIRE FILMARRAY TF Panel testing on these systems. Results from the BIOFIRE FILMARRAY TF Panel test are available within about one hour.

A test is initiated by loading Hydration into one port of the pouch and a whole blood or positive blood culture specimen mixed with the provided Sample Buffer into the port of the BIOFIRE FILMARRAY TF Panel pouch and placing it in a BIOFIRE System. The pouch contains all the reacents required for speciment testing 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 quides 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 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 (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. The solution is then distributed to each 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 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 document describes the BIOFIRE FILMARRAY Tropical Fever (TF) Panel, a rebranded version of the BioFire Global Fever Panel (K220870). The submission is a Special 510(k), indicating that the modifications are minor and do not affect the fundamental scientific technology, performance claims, or risk of the device. Therefore, the acceptance criteria and study proving its performance are based on the predicate device, the BioFire Global Fever Panel (K220870), as the performance claims of the rebranded panel remain identical.

1. Table of Acceptance Criteria and Reported Device Performance

Since this is a re-branding with identical performance claims, the "acceptance criteria" for the BIOFIRE FILMARRAY TF Panel are implicitly met by demonstrating substantial equivalence to the predicate device, which has already met its own acceptance criteria. The document states: "The performance claims of the BIOFIRE FILMARRAY TF Panel remain identical to the predicate BioFire Global Fever Panel."

Therefore, the performance data provided would be from the studies conducted for the predicate device, K220870 (BioFire Global Fever Panel). While the specific performance table demonstrating these results is not directly included in the provided text, the implication is that the predicate met the necessary performance metrics (e.g., sensitivity, specificity, accuracy for each target pathogen).

For illustrative purposes, if this were a new device submission, a table would look like this (conceptual, based on the device type):

The document explicitly states that the performance claims are identical to the predicate, meaning the predicate's performance metrics serve as the "acceptance criteria" implicitly met by this re-branding.

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

The provided text does not contain the specific sample sizes used for the clinical/test set for the predicate device (K220870). It also does not explicitly state the country of origin of the data or whether it was retrospective or prospective. Such details would typically be found in the original 510(k) submission for K220870 or its associated clinical study reports.

However, given it's a panel for tropical fevers, it's highly probable that the data would be from regions where these pathogens are endemic, and likely include both prospective and/or retrospective samples to
cover various disease states and prevalence.

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

For an in vitro diagnostic (IVD) device like the BIOFIRE FILMARRAY TF Panel, especially one that detects nucleic acids, the "ground truth" for the test set is typically established through a combination of:

• Clinical Diagnosis: Based on patient symptoms, travel history, other laboratory findings, and epidemiological data.
• Confirmatory Laboratory Testing: Often using highly sensitive and specific reference methods (e.g., CDC-validated PCR assays, sequencing, culture where applicable) for the target pathogens.

This process generally does not involve a "number of experts" in the same way an imaging AI ground truth would. Instead, it relies on validated laboratory methods and comprehensive clinical assessment. The qualifications would be laboratory professionals using validated reference methods and clinicians making diagnoses based on standard medical practice. The text does not provide specific details on the number or qualifications of experts involved in establishing ground truth for the predicate device.

4. Adjudication Method for the Test Set

As the ground truth for an IVD device like this is primarily established by laboratory reference methods and clinical outcomes, an "adjudication method" in the sense of multiple human readers resolving disagreements (common in imaging AI) is not directly applicable. The resolution of discrepancies would involve retesting by reference methods, review of patient charts, or further clinical investigation, rather than expert consensus reading of images.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done, and Effect Size

No, an MRMC comparative effectiveness study was not done, and is not applicable for this type of IVD device. MRMC studies are primarily used for medical imaging AI devices to assess the impact of AI assistance on human reader performance. This device is a qualitative, multiplexed PCR test that provides automated results, not an imaging diagnostic that assists human readers.

6. If a Standalone (i.e., Algorithm Only Without Human-in-the-Loop Performance) Was Done

Yes, the performance study for this device (or its predicate) is inherently a standalone performance assessment. The BIOFIRE FILMARRAY TF Panel is an automated test. The "algorithm" (the instrument's software interpreting PCR data) provides the final qualitative result (positive/negative for each pathogen) without a human interpreting raw data or images. The results are automatically interpreted and reported. The human "in the loop" is the lab technician who performs the test and interprets the results in a clinical context, but not one who influences the primary diagnostic output of the device itself.

The description explicitly states: "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 confirms its standalone nature.

7. The Type of Ground Truth Used

The ground truth for an IVD diagnostic like this is typically established by:

• Reference Laboratory Methods: Gold standard molecular assays (e.g., highly sensitive and specific PCR assays, sometimes developed or validated by national reference labs like the CDC), possibly combined with sequencing.
• Clinical Data and Outcomes: Patient symptoms, travel history, other clinical laboratory findings, and sometimes follow-up data to confirm true positive or true negative status.

The document states: "The BIOFIRE FILMARRAY TF Panel is not intended to be used as the sole basis for diagnosis, treatment, or other management decisions. Positive results do not rule out co-infection with other organisms... nor do negative results rule out infection. Negative results... may require additional testing if clinically indicated." This implies that while the device offers a direct result, the final clinical diagnosis relies on a broader set of information, and the device's performance is validated against established methods or confirmed clinical diagnoses.

8. The Sample Size for the Training Set

The document does not provide details on the training set for the algorithm (software). For PCR-based IVD devices, the "training" analogous to machine learning often involves significant laboratory work to:

• Design and optimize primers/probes: Extensive testing with known positive and negative samples, various concentrations of targets, and interfering substances.
• Establish cutoff values: For determining positive vs. negative results based on fluorescence thresholds and melt curve characteristics.
• Verify analytical performance: Limit of detection (LoD), inclusivity, exclusivity, cross-reactivity, precision, etc.

This "training" or development process heavily relies on characterized biological samples (clinically relevant strains, spiked samples, negative controls). The specific number of samples for each stage of this development is not given in this document, as it focuses on the equivalence to a predicate.

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

For IVD development, the ground truth for training/development samples is established through:

• Well-characterized Isolates/Strains: Using verified pathogen cultures or nucleic acid extracts with confirmed identity and quantification.
• Spiking Studies: Adding known amounts of target nucleic acids into clinical matrix (e.g., whole blood) from healthy donors.
• Known Clinical Samples: Samples previously characterized by highly accurate reference methods or confirmed clinical diagnosis.

This process ensures that the assay design (e.g., primer selection, PCR conditions, interpretation algorithms) effectively detects and differentiates the target pathogens from non-targets and in the presence of various confounding factors. The specific methodology for ground truth establishment for the training set of the predicate is not detailed in the provided text.

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 Pneumonia Panel (BIOFIRE Pneumonia Panel) is a multiplexed nucleic acid test intended for use with BIOFIRE FILMARRAY 2.0 (BIOFIRE 2.0) or BIOFIRE FILMARRAY TORCH (BIOFIRE TORCH) systems for the simultaneous detection of multiple respiratory viral and bacterial nucleic acids, as well as select antimicrobial resistance genes, in sputum-like speciorated sputum, or endotracheal aspirates) or bronchoalveolar lavage (BAL)-like specimens (BAL) obtained from individuals suspected of lower respiratory tract infection.

The following bacteria are reported semi-quantitatively with bins representing approximately 10^4, 10^5, or ≥10°7 genomic copies of bacterial nucleic acid per milliliter (copies/mL) of specimen, to aid in estimating relative abundance of nucleic acid from these common bacteria within a specimen:

Bacteria reported with bins of 10^4, 10^5, 10^6, or ≥10^7 copies/mL

• · Acinetobacter calcoaceticus-baumannii complex
• · Klebsiella oxytoca
• · Serratia marcescens
• · Enterobacter cloacae complex
• Klebsiella pneumoniae group
• · Staphylococcus aureus
• · Escherichia coli
• · Moraxella catarrhalis
• · Streptococcus agalactiae
• Haemophilus influenzae
• · Proteus spp.
• · Streptococcus pneumoniae
• Klebsiella aerogenes
• Pseudomonas aeruginosa
• · Streptococcus pyogenes

The following atypical bacteria, viruses, and antimicrobial resistance genes are reported qualitatively:

Atypical Bacteria

• Chlamydia pneumoniae
• · Legionella pneumophila
• Mycoplasma pneumoniae

Viruses

• · Adenovirus
• Human rhinovirus/enterovirus
• · Parainfluenza virus
• · Coronavirus
• · Influenza A virus
• Respiratory syncytial virus

• Human metapneumovirus

• Influenza B virus
  Antimicrobial Resistance Genes

• · CTX-M

• IMP

• КРС

• NDM

• OXA-48-like

• VIM

• · mecA/C and MREJ (MRSA)

The detection and identification of specific viral and bacterial nucleic acids, as well as the estimation of relative abundance of nucleic acid from common bacterial analytes, within specimens collected from individuals exhibiting signs and/or symptoms of a respiratory infection, aids in the diagnosis of lower respiratory infection with other clinical and epidemiological information. The results of this test should not be used as for diagnosis, treatment, or other patient management decisions.

Negative results in the setting of a respiratory illness may be due to infection with pathogens that are not detected by this test, pathogens below the limit of detection, or in the case of bacterial analytes, present at levels below the lowest reported 10^4 copies/mL bin. Detection of analytes does not rule out co-infection with other organisms; the agent(s) detected by the BIOFIRE Pneumonia Panel may not be the definite cause of disease. Additional laboratory testing (e.g. bacterial and viral culture, immunofluorescence, and radiography) may be necessary when evaluating a patient with possible lower respiratory tract infection.

Detection of bacterial nucleic acid may be indicative of colonizing or normal respiratory flora and may not indicate the causative agent of pneumonia. Semi-quantitative Bin (copies/mL) results generated by the BIOFIRE Pneumonia Panel are not equivalent to CFU/mL and do not consistently correlate with the quantity of bacterial analytes compared to CFU/mL. For specimens with multiple bacteria detected, the relative abundance of nucleic acids (copies/mL) may not correlate with the relative abundance of bacteria as determined by culture (CFU/mL). Clinical correlation is advised to determine significance of semi-quantitative Bin (copies/mL) for clinical management.

The antimicrobial resistance gene detected may or may not be associated with the agent(s) responsible for disease. Negative results for these antimicrobial resistance gene assays do not indicate susceptibility to corresponding classes of antimicrobials, as multiple mechanisms of antimicrobial resistance exist.

Antimicrobial resistance can occur via multiple mechanisms. A "Not Detected" result for a genetic marker of antimicrobial resistance does not indicate susceptibility to associated antimicrobial drugs or drug classes. A "Detected" result for a genetic marker of antimicrobial resistance cannot be definitively linked to the microorganism(s) detected. Culture is required to obtain isolates for antimicrobial susceptibility testing, and BIOFIRE Pneumonia Panel results should be used in conjunction with culture results for determination of bacterial susceptibility or resistance.

Due to the genetic similarity between human rhinovirus and enterovirus, the test cannot reliably differentiate them. A positive Rhinovirus/Enterovirus result should be followed up using an alternate method (e.g., cell culture or sequence analysis) if differentiation is required.

Culture is required to identify pathogens not detected by the BIOFIRE Pneumonia Panel, to further speciate analytes in genus, complex, or group results if desired, to identify bacterial pathogens present below the 10°4 copies/mL bin if desired, and for antimicrobial susceptibility testing.

BIOFIRE FILMARRAY Pneumonia Panel plus:

The BIOFIRE FILMARRAY Pneumonia Panel plus (BIOFIRE Pneumonia Panel plus) is a multiplexed nucleic acid test intended for use with BIOFIRE FILMARRAY 2.0 (BIOFIRE 2.0) or BIOFIRE FILMARRAY TORCH (BIOFIRE TORCH) systems for the simultaneous detection and identification of nucleic acids from Middle East respiratory syndrome coronavirus (MERS-CoV) and multiple respiratory viral and bacterial nucleic acids, as well as select antimicrobial resistance genes, in sputum-like specimens (induced or expectorated sputum, or endotracheal aspirates) or bronchoalveolar lavage (BAL)-like specimens (BAL or mini-BAL) obtained from individuals meeting MERS-CoV clinical and/or epidemiological criteria.

Testing with BIOFIRE Pneumonia Panel plus should not be performed unless the patient meets clinical and/or epidemiologic criteria for testing suspected MERS-CoV specimens. Thical signs and symptoms assocated with MERS-CoV infection, contact with a probable or confirmed MERS-CoV case, history of travel to geographic locations where MERS-CoV cases were detected, or other epidemiological links for which MERS-CoV testing may be indicated.

The following bacteria are reported semi-quantitatively with bins representing approximately 10^4, 10^5, or ≥10°7 genomic copies of bacterial nucleic acid per milliliter (copies/mL) of specimen, to aid in estimating relative abundance of nucleic acid from these common bacteria within a specimen:

Bacteria reported with bins of 10^4, 10^5, 10^6, or ≥10^7 copies/mL

• Acinetobacter calcoaceticus-baumannii complex
• Enterobacter cloacae complex
• Escherichia coli
• Haemophilus influenzae
• Klebsiella aerogenes
• · Klebsiella oxytoca
• · Klebsiella pneumoniae group
• Moraxella catarrhalis
• Proteus spp.
• Pseudomonas aeruginosa
• · Serratia marcescens
• Staphylococcus aureus
• Streptococcus agalactiae
• · Streptococcus pneumoniae
• · Streptococcus pyogenes

The following atypical bacteria, viruses, and antimicrobial resistance genes are reported qualitatively: Atypical Bacteria

• Chlamydia pneumoniae
• · Legionella pneumophila
• Mycoplasma pneumoniae

Viruses

• · Middle East respiratory syndrome coronavirus (MERS-CoV)
• Adenovirus
• Coronavirus
• Human metapneumovirus
• Human rhinovirus/enterovirus
• · Influenza A virus
• Influenza B virus
• Parainfluenza virus
• · Respiratory syncytial virus

Antimicrobial Resistance Genes

• CTX-M

• IMP

• · KPC

• NDM

• OXA-48-like

• VIM

• · mecA/C and MREJ (MRSA)

The detection and identification of specific viral and bacterial nucleic acids from MERS-CoV and other respiratory pathogens, as well as the estimation of relative abundance of nucleic acid from common bacterial analytes, within specimens collected from individuals meeting MERS-CoV clinical and/or epidemiological criteria aids in the differential diagnosis of MERS-CoV infection, if used in conjunction with other clinical and epidemiological information in accordance with the guidelines provided by the appropriate public health authorities.

BIOFIRE Pneumonia Panel plus MERS-CoV positive results are for the presumptive identification of MERS-CoV. The definitive identification of MERS-CoV requires additional testing and confirmation procedures in consultation with the appropriate public health authorities (e.g., local or state public health departments, etc.) for whom reporting is necessary. The diagnosis of MERS-CoV infection must be made based on history, signs, symptoms, exposure likelihood, and other laboratory evidence in addition to the identification of MERS-CoV.

BIOFIRE Pneumonia Panel plus MERS-CoV negative results, even in the context of a BIOFIRE Pneumonia Panel plus positive result for one or more of the common respiratory pathogens, do not preclude MERS-CoV infection and should not be used as the sole basis for patient management decisions. The levels of MERS-CoV that would be present in sputum-like or BAL-like specimens from individuals with early infection and from asymptomatic MERS-CoV carriers are not well understood. A negative BIOFIRE Pneumonia Panel plus MERS-CoV result in an asymptomatic individual does not rule out the possibility of future illness and does not demonstrate that the individual is not infectious.

Viral culture should not be attempted on specimens with positive BIOFIRE Pneumonia Panel plus results for MERS-CoV unless a BSL 3 facility is available to receive and culture specimens.

Negative results in the setting of a respiratory illness may be due to infection with pathogens that are not detected by this test, pathogens below the limit of detection, or in the case of bacterial analytes, present at levels below the lowest reported 10^4 copies/mL bin. Detection of analytes does not rule out co-infection with other organisms; the agent(s) detected by the BIOFIRE Pneumonia Panel plus may not be the definite cause of disease. Additional laboratory testing (e.g. bacterial and viral culture, immunofluorescence, and radiography) may be necessary when evaluating a patient with possible lower respiratory tract infection.

Detection of bacterial nucleic acid may be indicative of colonizing or normal respiratory flora and may not indicate the causative agent of pneumonia. Semi-quantitative Bin (copies/mL) results generated by the BIOFIRE Pneumonia Panel plus are not equivalent to CFU/mL and do not consistently correlate with the quantity of bacterial analytes compared to CFU/mL. For specimens with multiple bacteria detected, the relative abundance of nucleic acids (copies/mL) may not correlate with the relative abundance of bacteria as determined by culture (CFU/mL). Clinical correlation is advised to determine significance of semi-quantitative Bin (copies/mL) for clinical management.

The antimicrobial resistance gene detected may or may not be associated with the agent(s) responsible for disease. Negative results for these antimicrobial resistance gene assays do not indicate susceptibility to corresponding classes of antimicrobials, as multiple mechanisms of antimicrobial resistance exist.

Antimicrobial resistance can occur via multiple mechanisms. A "Not Detected" result for a genetic marker of antimicrobial resistance does not indicate susceptibility to associated antimicrobial drugs or drug classes. A "Detected" result for a genetic marker of antimicrobial resistance cannot be definitively linked to the microorganism(s) detected. Culture is required to obtain isolates for antimicrobial susceptibility testing, and BIOFIRE Pneumonia Panel plus results should be used in conjunction with culture results for determination of bacterial susceptibility or resistance.

Due to the genetic similarity between human rhinovirus and enterovirus, the test cannot reliably differentiate them. A positive Rhinovirus/Enterovirus result should be followed up using an alternate method (e.g., cell culture or sequence analysis) if differentiation is required.

Culture is required to identify pathogens not detected by the BIOFIRE Pneumonia Panel plus, to further speciate analytes in genus, complex, or group results if desired, to identify bacterial pathogens present below the 10°4 copies/mL bin if desired, and for antimicrobial susceptibility testing.

The BIOFIRE® FILMARRAY® Pneumonia Panel and BIOFIRE® FILMARRAY® Pneumonia Panel plus use nested, multiplex reverse transcription polymerase chain reaction (PCR), followed by melting curve analysis for the detection of select organisms and antimicrobial resistance (AMR) genes in sputum-like (induced and expectorated sputum as well as endotracheal aspirate, ETA) and bronchoalveolar lavage (BAL)-like (BAL and mini-BAL) specimens. The panels allow for the identification of specific bacteria, atypical bacteria, viruses, and AMR genes as indicated in Table 1. The BIOFIRE Pneumonia Panel and BIOFIRE Pneumonia Panel plus pouches are identical, but the BIOFIRE Pneumonia Panel plus includes reporting of Middle East Respiratory Syndrome Coronavirus (MERS-CoV), which is not included in the BIOFIRE Pneumonia Panel. Reporting of MERS-CoV is controlled through software masking of the MERS-CoV result for the BIOFIRE Pneumonia Panel.

The BIOFIRE Pneumonia Panels are compatible with bioMérieux's PCR-based in vitro diagnostic BIOFIRE® FILMARRAY® 2.0 and BIOFIRE® FILMARRAY® TORCH Systems for infectious disease testing. Specific software module (i.e. BIOFIRE Pneumonia Panel Pouch Module Software) are used to perform BIOFIRE Pneumonia Panels testing on these systems.

This document refers to a 510(k) premarket notification for a medical device (BIOFIRE FILMARRAY Pneumonia Panel and BIOFIRE FILMARRAY Pneumonia Panel plus). This type of submission focuses on demonstrating substantial equivalence to a legally marketed predicate device rather than presenting a full de novo study with strict acceptance criteria and performance validation against a test set. The document clearly states that the submission is for software updates to mitigate false positive Coronavirus and CTX-M results and that "Reanalysis of the performance data with the modified pouch module software did not result in an overall change of the study conclusions or performance claims for non-clinical/analytical studies."

Therefore, the information typically requested in your prompt regarding acceptance criteria, study details, sample sizes, expert ground truth establishment, MRMC studies, and standalone performance might not be explicitly detailed in this type of FDA submission as it would be for a de novo marketing authorization. However, I can extract what is available and clarify what is not.

Based on the provided text, here's a breakdown of the requested information:

1. A table of acceptance criteria and the reported device performance

The document does not explicitly state formal "acceptance criteria" in a quantitative table format as might be seen for a new device submission. Instead, the focus is on the impact of the software update on existing performance. The relevant performance change mentioned is:

The document implies that these updated specificities are acceptable because they represent an improvement in mitigating false positives and "did not result in an overall change of the study conclusions or performance claims for non-clinical/analytical studies."

2. Sample sizes used for the test set and the data provenance (e.g. country of origin of the data, retrospective or prospective)

The document mentions a "Clinical Prospective Study" for which the Coronavirus specificity numbers are reported. It does not provide the exact sample size for this specific study, nor does it explicitly state the country of origin. It indicates that the reanalysis of existing performance data was done.

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)

This information is not provided in the document. As this is a molecular diagnostic test, ground truth would typically be established by highly sensitive and specific laboratory methods (e.g., PCR, sequencing, culture) rather than expert human interpretation in the way radiologists interpret images.

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

This information is not provided.

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

An MRMC study is not applicable here as this is a molecular diagnostic device, not an AI-assisted diagnostic imaging device that involves human reader interpretation.

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

This refers to the performance of the assay itself. The document implicitly discusses the "standalone" performance of the BIOFIRE FILMARRAY Pneumonia Panel and Panel Plus, which is a molecular diagnostic test. The reported specificities are a measure of this standalone performance. The software update is an internal modification to the assay's interpretation logic.

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

The document implies that the ground truth for the clinical performance evaluations was established through highly sensitive and specific methods for pathogen detection, as is standard clinical laboratory practice for molecular diagnostics. It does not explicitly state the specific ground truth methods but mentions that "Culture is required to obtain isolates for antimicrobial susceptibility testing, and BIOFIRE Pneumonia Panel results should be used in conjunction with culture results for determination of bacterial susceptibility or resistance." This suggests that culture and other definitive laboratory tests would be part of the ground truth establishment, particularly for bacterial analytes and antimicrobial resistance genes.

8. The sample size for the training set

This document describes a software update to an already cleared device. It does not provide details about a "training set" in the context of machine learning model development. The software update appears to be a rule-based or algorithmic adjustment to optimize melting curve analysis and mitigate cross-reactivity with human genomic DNA, rather than a re-training of a complex AI model. The modification was driven by "routine post-market monitoring and complaint investigations combined with concurrent findings from an internal product development study."

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

As there's no mention of a traditional "training set" in the context of an AI model, this information is not provided. The "ground truth" that informed the software change was likely observations of false positives in clinical samples, identified through investigations and potentially confirmed by orthogonal testing or characterization of the offending interactions (cross-reactivity with hgDNA).

Ask a specific question about this device

The BIOFIRE® SPOTFIRE® Respiratory/Sore Throat (R/ST) Panel Mini is a multiplexed polymerase chain reaction (PCR) test intended for use with the BIOFIRE® System for the simultaneous, qualitative detection and identification of multiple respiratory viral and bacterial nucleic acids in nasopharyngeal swab (NPS) specimens obtained from individuals with signs and symptoms of respiratory tract infection, including COVID-19; (Respiratory menu) or in throat swab (TS) specimens from individuals with signs and symptoms of pharyngitis (Sore Throat menu).

The following analytes are identified and differentiated using the SPOTFIRE R/ST Panel Mini:

Respiratory Menu:
Viruses
Coronavirus SARS-CoV-2
Human rhinovirus
Influenza A virus
Influenza B virus
Respiratory syncytial virus

Sore Throat Menu:
Viruses
Human rhinovirus
Influenza A virus
Influenza B virus
Respiratory syncytial virus
Bacteria
Streptococcus pyogenes (group A Strep)

Nucleic acids from the viral and bacterial organisms identified by this test are generally detectable in NPS/TS specimens during the acute phase of infection. The detection and identification of specific viral and bacterial nucleic acids from individuals exhibiting signs and symptoms of respiratory infection and/or pharyngitis is indicative of the presence of the identified microorganism and aids in diagnosis if used in conjunction with other clinical and epidemiological information, and laboratory findings. The results of this test should not be used as the sole basis for diagnosis, treatment, or other patient management decisions.

Negative results in the setting of a respiratory illness and/or pharyngitis may be due to infection with pathogens that are not detected by this test, or a respiratory tract infection that may not be detected by an NPS or TS specimen. Positive results do not rule out co-infection with other organisms. The agent(s) detected by the SPOTFIRE R/ST Panel Mini may not be the definite cause of disease.

Additional laboratory testing (e.g., bacterial and viral culture, immunofluorescence, and radiography) may be necessary when evaluating a patient with possible respiratory tract infection and/or pharyngitis.

The SPOTFIRE R/ST Panel Mini simultaneously identifies 5 different respiratory viral pathogens in nasopharyngeal swabs (NPS) or 5 different viral and bacterial pharyngitis pathogens in throat swabs (TS) from individuals with signs and symptoms of respiratory tract infections or pharyngitis, respectively, (see Table 1) The SPOTFIRE R/ST Panel Mini is compatible with the BIOFIRE® System, a polymerase chain reaction (PCR)-based in vitro diagnostic system for infectious disease testing. The BIOFIRE System Sottware executes the SPOTFIRE R/ST Panel Mini test and interprets and reports the test results. The SPOTFIRE R/ST Panel Mini was designed to be used in CLIA-waived environments.

A test is initiated by loading Hydration Solution injection solution injection port of the SPOTFIRE R/ST Panel Mini pouch and NPS or TS specimen, mixed with the provided Sample injection port of the SPOTFIRE R/ST Panel Mini pouch and placing it in the SPOTFIRE System. The reagents required for specimen testing and analysis in a freeze-dried format; the addition of Hydration and Sample/Buffer Mix rehydrates the reagents. After the pouch is prepared, the SPOTFIRE System Software guides the user through the steps of placing the pouch into the instrument, scanning the sample identification, and initiating the run.

The SPOTFIRE System contains coordinated systems 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 SPOTFIRE R/ST Panel Mini pouch using mechanical Ivsis followed by purfication using standard magnetic bead technology. After extracting and purifying nucleic acids from the unprocessed sample, the SPOTFIRE System performs a nested multiplex PCR that is executed in two stage. During the first stage, the SPOTFIRE 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 doublestranded 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 singleplex fashion in each well of the array. At the conclusion 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 SPOTFIRE System 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 SPOTFIRE R/ST Panel Mini.

This document describes the BIOFIRE® SPOTFIRE® Respiratory/Sore Throat (R/ST) Panel Mini, a multiplex PCR test.

1. Table of Acceptance Criteria and Reported Device Performance

The document provides extensive analytical performance data rather than a direct comparison of acceptance criteria to reported clinical performance metrics (like PPA and NPA). However, the "Summary of Performance Data" for clinical studies does present sensitivity/PPA and specificity/NPA, which can be interpreted as the reported device performance against implied clinical acceptance criteria.

Clinical Performance Summary (NPS Specimens - Respiratory Menu)

Clinical Performance Summary (TS Specimens - Sore Throat Menu)

Analytical Acceptance Criteria and Results for key studies:

2. Sample Sizes and Data Provenance

• Clinical Performance (Test Set):
  • NPS Specimens (Respiratory Menu - Prospective): Total of 1115 specimens. The document doesn't explicitly state the country of origin but implies clinical sites (e.g., "as tested by intended users"). This is prospective data.
  • NPS Specimens (Respiratory Menu - Archived): Used for some analytes, e.g., Human Rhinovirus (30 positive, 454 negative), Influenza A (59 positive, 423 negative), Influenza B (30 positive, 28 negative), RSV (37 positive, 447 negative). This is retrospective data.
  • TS Specimens (Sore Throat Menu - Prospective): Total of 876 specimens for most viral targets. Streptococcus pyogenes had 217 positive (PCR) / 177 positive (Culture) and 660 negative (PCR) / 692 negative (Culture). This is prospective data.
  • TS Specimens (Sore Throat Menu - Archived): Used for some analytes, e.g., Human Rhinovirus (2 positive, 57 negative), Influenza A (11 positive, 44 negative), Influenza B (20 positive, 0 negative), RSV (2 positive, 57 negative), Streptococcus pyogenes (39 positive, 10 negative). This is retrospective data.
  • TS Specimens (Sore Throat Menu - Contrived): Used for some analytes, e.g., Influenza A (93 positive, 332 negative), Influenza B (49 positive, 333 negative), RSV (50 positive, 381 negative). This would be laboratory-generated data.

3. Number of Experts and Qualifications for Ground Truth

The document does not specify the number or qualifications of experts used to establish the ground truth for the clinical test set. It mentions using "molecular assays or known specimen composition" as comparator methods for most analytes, and "culture" as the reference method for Streptococcus pyogenes.

4. Adjudication Method

The document does not describe any specific adjudication method (e.g., 2+1, 3+1) for establishing the ground truth or resolving discrepancies in the clinical test set.

5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study

No MRMC comparative effectiveness study is mentioned or implied, as this device is an in vitro diagnostic (IVD) PCR test for direct pathogen detection, not an AI-assisted diagnostic imaging or interpretation tool for human readers. Therefore, the concept of "human readers improve with AI vs without AI assistance" does not apply.

6. Standalone Performance

Yes, the studies described are for standalone performance. The BIOFIRE® SPOTFIRE® R/ST Panel Mini provides automated interpretation and reporting of test results based on the PCR assay. It is designed to be used independently to generate a qualitative detection and identification of microbial nucleic acids.

7. Type of Ground Truth Used

• Clinical Performance (Prospective/Archived): The ground truth for most analytes was established using molecular assays or, in some cases, known specimen composition. For Streptococcus pyogenes, culture was also used as a reference method for some comparisons.
• Analytical Performance (LoD, Inclusivity, Exclusivity, Interference, Reproducibility, Matrix Validation, Transport Media Validation, Carry Over): The ground truth was established through known specimen composition (e.g., contrived samples with known concentrations of organisms, presence of interfering substances, specific transport media).

8. Sample Size for the Training Set

The document does not explicitly mention a "training set" in the context of machine learning or AI algorithm development. This device is a PCR-based test, and its performance is validated through analytical and clinical studies, not typically through a machine learning training phase with a distinct dataset. The "training" in this context refers to the development and optimization of the PCR primers, probes, and reaction conditions.

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

Given that this is a PCR diagnostic device, not an AI algorithm in the typical sense of needing a "training set" for model learning, this question isn't directly applicable. The "ground truth" for developing and optimizing the PCR assays themselves would have been established through:

• Careful selection and validation of synthetic nucleic acid targets.
• Testing with characterized microbial isolates and clinical samples whose status was confirmed by established reference methods (e.g., sequencing, culture, validated molecular tests).
• In silico analysis of genetic sequences to design primers and probes with high specificity and inclusivity.

Ask a specific question about this device

The BIOFIRE® SPOTFIRE® Respiratory/Sore Throat (R/ST) Panel is a multiplexed polymerase chain reaction (PCR) test intended for use with the BIOFIRE® System for the simultaneous, qualitative detection and identification of multiple respiratory viral and bacterial nucleic acids in nasopharyngeal swab (NPS) specimens obtained from individuals with signs and symptoms of respiratory tract infection, including COVID-19; (Respiratory menu) or in throat swab (TS) specimens from individuals with signs and symptoms of pharyngitis (Sore Throat menu).

The following organism types and subtypes are identified and differentiated using the SPOTFIRE R/ST Panel:

Respiratory Menu Viruses Adenovirus Coronavirus SARS-CoV-2 Coronavirus (seasonal) Human metapneumovirus Human rhinovirus/enterovirus Influenza A virus Influenza A virus/H1-2009 Influenza A virus/ H3 Influenza B virus Parainfluenza virus Respiratory syncytial virus

• Bacteria Bordetella parapertussis Bordetella pertussis Chlamydia pneumoniae Mycoplasma pneumoniae
  Sore Throat Menu Viruses Adenovirus Coronavirus (seasonal) Human metapneumovirus Human rhinovirus/enterovirus Influenza A virus Influenza A virus/H1-2009 Influenza A virus/H3 Influenza B virus Parainfluenza virus Respiratory syncytial virus

Bacteria Chlamydia pneumoniae Mycoplasma pneumoniae Streptococcus dysgalactiae (Group C/G Strep) Streptococcus pyogenes (Group A Strep)

Nucleic acids from the viral and bacterial organisms identified by this test are generally detectable in NPS/TS specimens during the acute phase of infection and identification of specific viral and bacterial nucleic acids from individuals exhibiting signs and symptoms of respiratory infection and/or pharyngtis are indicative of the identified microorganism and aids in diagnosis if used in conjunction with other clinical and epidemiological information, and laboratory findings. The results of this test should not be used as the sole basis for diagnosis, treatment, or other patient management decisions.

Negative results in the setting of a respiratory illness and/or pharyngitis may be due to infection with pathogens that are not detected by this test, or a respiratory tract infection that may not be detected by an NPS or TS specimen. Positive results do not rule out coinfection with other organisms. The agent(s) detected by the SPOTFIRE R/ST Panel may not be the definite cause of disease.

Additional laboratory testing (e.g., bacterial and viral culture, immunofluorescence, and radiography) may be necessary when evaluating a patient with possible respiratory tract infection and/or pharyngitis.

The SPOTFIRE R/ST Panel simultaneously identifies 15 different respiratory viral and bacterial pathogens in nasopharyngeal swabs (NPS) or 14 viral and bacterial pharyngitis pathogens in throat swabs (TS) from individuals with signs and symptoms of respiratory tract infections or pharyngitis, respectively, (see Intended Use:). The SPOTFIRE R/ST Panel is compatible with the SPOTFIRE System, a polymerase chain reaction (PCR)-based in vitro diagnostic system for infectious disease testing. The SPOTFIRE System Software executes the SPOTFIRE R/ST Panel test and interprets and reports the test results. The SPOTFIRE RIST Panel was designed to be used in CLIA-waived environments. A test is initiated by loading Hydration Solution into one port of the SPOTFIRE R/ST Panel pouch and NPS or TS specimen, mixed with the provided Sample Buffer, into the port of the SPOTFIRE R/ST Panel pouch and placing it in the SPOTFIRE System. 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 SPOTFIRE System Software guides the user through the steps of placing the instrument, scanning the pouch barcode, entering the sample identification, and initiating the run.

The SPOTFIRE System contains coordinated systems of inflatable bladders and seal points, which act on the pouch to control the movement of liguid between the pouch blisters. When a bladder is inflated over a reagent blister, it forces liguid 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 and cooling of the pouch to drive the PCR reactions and the melt curve analysis.

Nucleic acid extraction occurs within the SPOTFIRE R/ST Panel 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 SPOTFIRE System performs a nested multiplex PCR that is executed in two stage, the SPOTFIRE 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 doublestranded 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, is performed in singleplex fashion in each well of the array. At the conclusion 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 SPOTFIRE System Software automatically interprets the results of each DNA met curve analysis and combines the data with the results of the internal pouch controls to provide a test result for each organism on the SPOTFIRE R/ST Panel.

Here's a breakdown of the acceptance criteria and study proving the device meets those criteria, based on the provided FDA 510(k) summary for the BIOFIRE® SPOTFIRE® Respiratory/Sore Throat (R/ST) Panel:

The document describes the BIOFIRE® SPOTFIRE® Respiratory/Sore Throat (R/ST) Panel, a multiplexed PCR test for simultaneous, qualitative detection and identification of multiple respiratory viral and bacterial nucleic acids. The data presented primarily focuses on analytical performance and clinical performance to demonstrate substantial equivalence to a predicate device.

1. Table of Acceptance Criteria and Reported Device Performance

The acceptance criteria are generally implied by the performance metrics reported, specifically the Positive Percent Agreement (PPA) / Sensitivity and Negative Percent Agreement (NPA) / Specificity. For analytical studies, acceptance criteria related to percentages of positive results and agreement levels are explicitly stated.

Clinical Performance Acceptance Criteria (Implied by Data Reported):
For each analyte, the acceptance criteria are generally to achieve high PPA and NPA. While specific numerical thresholds for PPA/NPA are not explicitly listed as "acceptance criteria" in the clinical tables themselves, the FDA's clearance implies that the presented performance met their internal requirements for substantial equivalence. For diagnostic tests, generally, PPA and NPA values in the high 90s are expected.

Analytical Performance Acceptance Criteria and Reported Performance:

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

The sample sizes vary by analyte and study type (prospective, archived, contrived).

• Clinical Performance (Test Set):

  • NPS Specimens (Respiratory Menu):
    • Prospective Data: The total number of NPS specimens tested across all viruses and bacteria is not explicitly stated as a single number but can be aggregated from the "Positive" and "Negative" counts for each analyte. For example, for Adenovirus, there were 33 positives and 1082 negatives, totaling 1115 prospective NPS specimens where Adenovirus was assessed. This appears to be the total number of clinical samples evaluated in the prospective study.
    • Archived Data: Similarly, for Adenovirus, there were 31 positives and 439 negatives, totaling 470 archived NPS specimens.
    • Contrived Data: Indicated as 0/0 for all NPS analytes, suggesting contrived samples were not used for clinical performance evaluation of NPS specimens.
  • TS Specimens (Sore Throat Menu):
    • Prospective Data: For Adenovirus, 65 positives and 810 negatives (total 875). This seems to be the total number of clinical throat swab specimens assessed.
    • Archived Data: For Adenovirus, 11 positives and 48 negatives (total 59).
    • Contrived Data: For Adenovirus, 50 positives and 381 negatives (total 431). Contrived samples were used for TS clinical performance studies.
  • Data Provenance: The document states "as tested by intended users," implying clinical sites. No specific country of origin is mentioned, but typically, these studies for FDA clearance involve sites within the US. The "Prospective" studies indicate prospective collection, while "Archived" refers to retrospective samples. "Contrived" samples are laboratory-prepared.

• Analytical Performance (Test Set):

  • Limit of Detection (LoD): At least 20 replicates (e.g., 19/20) tested at LoD and 10-fold below LoD for each analyte.
  • Analytical Reactivity (Inclusivity): 3/3 or 4/5 replicates tested within 10x LoD for each isolate.
  • Near-LoD/Reproducibility: Not explicitly stated but mentions "multiple days," "multiple operators," "three unique SPOTFIRE Systems," "three distinct clinical sites holding a CLIA waiver." The reported positive and negative agreement totals are 2070 (BioFire) and 1380 (clinical sites) tests.

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 or their qualifications (e.g., radiologist with 10 years of experience) used to establish the ground truth. This is a common characteristic of in vitro diagnostic (IVD) submissions focusing on molecular diagnostic tests.

• For molecular tests, the "ground truth" is typically established by comparator methods, often laboratory-developed tests (LDTs) or other cleared/validated molecular diagnostic assays (e.g., PCR followed by sequencing, or highly sensitive and specific reference PCR methods).
• For bacterial culture (used for Streptococcus dysgalactiae and Streptococcus pyogenes), the ground truth is established by standard microbiological culture and identification techniques, performed by trained laboratory personnel.

4. Adjudication Method for the Test Set

The document does not describe a formal adjudication method (e.g., 2+1, 3+1) for the clinical test sets. This is expected given that the ground truth is established by laboratory reference methods (molecular or culture), which typically do not involve human reader adjudication in the same way imaging studies might. Any discrepancies between the investigational device and the reference method would be investigated by the manufacturer, rather than through an expert consensus adjudication.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done

No, an MRMC comparative effectiveness study was not done. This type of study is primarily relevant for imaging-based AI devices where human readers interpret medical images, and the AI assists or augments their performance. The BIOFIRE SPOTFIRE R/ST Panel is a molecular diagnostic test where the output is an automated detection of nucleic acids, not an interpretation by a human reader that could be augmented by AI.

6. If a Standalone (i.e. Algorithm Only Without Human-in-the Loop Performance) Was Done

Yes, the performance data presented (Tables 2 and 3 for Clinical Performance, and Table 4 for Analytical Performance) represents the standalone performance of the BIOFIRE SPOTFIRE R/ST Panel, which includes the instrument and its automated software interpretation. The device itself is designed to provide automated results without human interpretive input for the detection of targets. The "as tested by intended users" for clinical performance indicates that the device was used in a realistic setting, but the performance metrics reflect the direct output of the system.

7. The Type of Ground Truth Used

The ground truth for the clinical performance evaluation was established using:

• Comparator molecular assays or known specimen composition for most analytes (referred to as "molecular assays or known specimen composition were used as comparator methods" for PPA/NPA). This suggests a combination of validated PCR assays, and potentially sequencing for confirmation.
• Culture for Streptococcus dysgalactiae (Group C/G Strep) and Streptococcus pyogenes (Group A Strep). This is explicitly stated: "Performance measures of sensitivity and specificity refer to the prospective and archived Streptococcus and archived Streptococcus analytes for which culture was used as the reference method."

For analytical studies, the ground truth was established by:

• Known concentrations of organisms (e.g., viable or infectious units, nucleic acid copies/mL) for LoD and Inclusivity studies.
• Defined panels of organisms or substances for Exclusivity and Interference studies.

8. The Sample Size for the Training Set

This document does not provide information on the training set size directly. The presented studies are for validation/testing of the device's performance. For molecular diagnostic assays like this, the 'training' of the algorithms (e.g., primer design, melt curve analysis interpretation) typically happens during the assay development phase, often using synthetic targets, cultured organisms, and preliminary clinical samples. However, this is not detailed in a 510(k) summary, which focuses on validation data against a defined product. The "software was verified and validated" statement implies that developmental data was used, but details on sample size for that specific phase are not provided in this regulatory summary.

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

Since the training set details are not provided, the method for establishing its ground truth is also not explicitly stated in this document. However, based on typical IVD development practices:

• Ground truth for assay development (which informs the 'training' of a molecular diagnostic system) would involve well-characterized positive and negative controls, reference strains, and potentially sequenced clinical isolates.
• Molecular target sequences (in silico analysis)
• Analytical dilution series where the exact concentration of the pathogen is known.
• Samples confirmed by multiple, orthogonal laboratory methods.

The rigorous analytical and clinical studies described in the results section serve as the validation of the final trained/developed system.

Ask a specific question about this device

The BIOFIRE® SPOTFIRE® Respiratory (R) Panel Mini) is a multiplexed polymerase chain reaction (PCR) test intended for use with the BIOFIRE® SPOTFIRE® System for the simultaneous, qualitative detection and identification of multiple respiratory viral nucleic acids in nasopharyngeal swab (NPS) specimens obtained from individuals with signs and symptoms of respiratory tract infection, including COVID-19.

The following organism types and subtypes are identified and differentiated using the SPOTFIRE R Panel Mini:

• Coronavirus SARS-CoV-2
• · Human rhinovirus
• · Influenza A virus
• · Influenza B virus
• · Respiratory syncytial virus

Nucleic acids from the viral organisms identified by this test are generally detectable in NPS specimens during the acute phase of infection. The detection of specific viral nucleic acids from individuals exhibiting signs and/or symptoms of respiratory infection are indicative of the identified microorganism and aids in diagnosis if used in conjunction with other clinical and epidemiological information findings. The results of this test should not be used as the sole basis for diagnosis, treatment, or other patient management decisions.

Negative results in the setting of a respiratory illness may be due to infection with pathogens that are not detected by this test, or lower respiratory tract infection that may not be detected by an NPS specimen. Positive results do not rule out coinfection with other organisms. The agent(s) detected by the SPOTFIRE R Panel Mini may not be the definite cause of disease.

Additional laboratory testing (e.g., bacterial and viral culture, immunofluorescence, and radiography) may be necessary when evaluating a patient with possible respiratory tract infection.

The BIOFIRE SPOTFIRE Respiratory (R) Panel Mini simultaneously identifies five different respiratory viral pathogens in nasopharyngeal swabs (NPS) from individuals with signs and symptoms of respiratory tract infection (see Table 1). The SPOTFIRE R Panel Mini is compatible with the BIOFIRE® System, a polymerase chain reaction (PCR)-based in vitro diagnostic system for infectious disease testing. The BIOFIRE System Software executes the SPOTFIRE R Panel Mini test and interprets and reports the test results.

A test is initiated by loading Hydration into one port of the SPOTFIRE R Panel Mini pouch and NPS specimen mixed with the provided Sample Buffer into the other port of the SPOTFIRE R Panel Mini pouch and placing it in the SPOTFIRE System. The pouch contains all of the reagents required for speciment 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 SPOTFIRE System Software quides the user through the pouch into the instrument, scanning the pouch barcode, entering the sample identification, and initiating the run.

The SPOTFIRE System contains coordinated systems 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 liguid 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 Peltier and cooling of the pouch to drive the PCR reactions and the melt curve analysis.

Nucleic acid extraction occurs within the SPOTFIRE R Panel Mini pouch using mechanical lysis followed by purification using standard magnetic bead technology. After extracting and purifying nucleic acids from the unprocessed sample, the SPOTFIRE System performs a nested multiplex PCR that is executed in two stage, the SPOTFIRE 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 doublestranded 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 singleplex fashion in each well of the array. At the conclusion 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 SPOTFIRE System 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 BIOFIRE® SPOTFIRE® Respiratory (R) Panel Mini, a PCR test for detecting respiratory viral nucleic acids. However, the document, being a Special 510(k) Summary, focuses on demonstrating substantial equivalence to a predicate device (BIOFIRE® SPOTFIRE® Respiratory (R) Panel) rather than providing detailed, de novo performance study results against specific acceptance criteria.

The key statement regarding performance data is:
"The performance data for the SPOTFIRE R Panel Mini is identical to the SPOTFIRE R Panel (K213954), but only contains data for the five analytes detected by the SPOTFIRE R Panel Mini (Coronavirus SARS-CoV-2, human rhinovirus, influenza A virus, influenza B virus, and respiratory syncytial virus). Please see the BIOFIRE Respiratory Panel Mini Instructions for Use for performance tables."

This indicates that the performance of the Mini Panel relies on the studies conducted for the full Panel. To fully answer your request, the "BIOFIRE Respiratory Panel Mini Instructions for Use" would be needed, as that is where the detailed performance tables (which would contain acceptance criteria and reported performance) are referenced.

Based on the provided text, here's what can be extracted and what cannot be:

Since the document directly states that the performance data for the Mini Panel is identical to the full Panel for the relevant analytes, and directs to the Instructions for Use for details, it implies that no new, separate, full-scale clinical study was conducted for the Mini Panel. Instead, the justification for meeting acceptance criteria is based on the performance of the predicate device.

Extracted Information from the Provided Document:

1. A table of acceptance criteria and the reported device performance:

• Cannot be fully provided from this document. The document states: "Please see the BIOFIRE Respiratory Panel Mini Instructions for Use for performance tables." This means the specific acceptance criteria and reported performance values (like sensitivity, specificity, accuracy) are not contained within this 510(k) summary directly.

2. Sample size used for the test set and the data provenance (e.g., country of origin of the data, retrospective or prospective):

• Cannot be fully provided from this document. This information would be detailed in the performance study section of the predicate device's submission or its Instructions for Use, which is not included here. The document only states that the performance data for the Mini Panel is "identical" to the predicate for the five analytes.

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 / Cannot be provided. This device is an in vitro diagnostic (IVD) PCR test, not an imaging AI device. Ground truth for IVD tests is typically established through reference methods (e.g., highly sensitive PCR assays, culture, sequencing) on clinical samples, not by expert readers or adjudicators in the way it's done for medical imaging. The concept of "experts" as in radiologists is thus not relevant here.

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

• Not applicable. As stated above, this is an IVD PCR device. Adjudication methods like 2+1 or 3+1 are typically used for establishing ground truth in image interpretation studies where human experts disagree. For PCR tests, discordance resolution might occur by running a different highly sensitive reference method, but it's not "adjudication" in the sense used for human image interpretation.

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 is an in vitro diagnostic (IVD) PCR test, not an AI medical imaging device that assists human readers. There are no "human readers" interpreting images to be assisted by this device.

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

• Yes, for the predicate device. The BIOFIRE SPOTFIRE system, including this Mini Panel, functions as a standalone diagnostic test providing a qualitative result (positive/negative for each pathogen). Its performance (sensitivity, specificity, accuracy) is inherently assessed in a standalone manner, separate from human interpretation of the raw PCR data/results. The "algorithm" here is the system's software that interprets the PCR melt curve analysis and internal controls to provide a final diagnostic result.

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

• Reference molecular methods / clinical diagnosis. For IVD PCR tests, ground truth for clinical samples is typically established by comparing the device's results to a highly sensitive and specific reference molecular method (e.g., another FDA-cleared or laboratory-developed PCR assay, often employing bi-directional sequencing for confirmation) applied to the same or split clinical samples. This is implicitly what happens for the predicate device's performance studies. The overall diagnosis for a patient would then integrate this with other clinical and epidemiological information. Clinical outcomes data or pathology are not typically the primary ground truth for direct pathogen detection performance of a PCR test.

8. The sample size for the training set:

• Not explicitly stated in this document. For IVD PCR devices, the "training set" doesn't strictly apply in the sense of machine learning model training on large datasets. Instead, it refers to samples used during the development and optimization phases of the assay. This information is confidential and not typically disclosed in a 510(k) summary. The focus for this submission is on demonstrating that the modified software for the Mini Panel (which just filters results from the existing R Panel) has been "verified and validated to show no change in safety and effectiveness," implying no new large-scale training was needed.

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

• Not explicitly stated/applicable in the ML sense. As above, "training set" for PCR development involves using characterized samples (e.g., spiked samples, clinical samples with known positivity/negativity determined by reference methods) to optimize assay parameters. The exact methodology would be part of the intellectual property of the manufacturer and documented internally.

Summary of Acceptance Criteria and Study Proof (as much as inferred from the document):

Given the nature of this submission as a "Special 510(k)," the core proof for the device meeting acceptance criteria is its substantial equivalence to the predicate BIOFIRE® SPOTFIRE® Respiratory (R) Panel (K213954). The acceptance criteria for the Mini Panel are, by this logic, implicitly met if the performance for the shared analytes (Coronavirus SARS-CoV-2, human rhinovirus, influenza A virus, influenza B virus, and respiratory syncytial virus) is identical to the already cleared predicate device.

The study that proves the device meets the acceptance criteria is effectively the original clinical performance study conducted for the predicate BIOFIRE® SPOTFIRE® Respiratory (R) Panel (K213954).
The specific data, including sensitivity, specificity, positive predictive value, and negative predictive value, along with the sample types and sizes from those studies, would be found in the Indications for Use or similar performance summary section of the K213954 submission or its final labeling.

The current document confirms that:

• The Mini Panel is an identical product to the full Panel, with modified labeling and software to report only five of the 15 analytes.
• The modified software has been "verified and validated to show no change in safety and effectiveness."
• "The performance data for the SPOTFIRE R Panel Mini is identical to the SPOTFIRE R Panel (K213954), but only contains data for the five analytes detected by the SPOTFIRE R Panel Mini."

Therefore, the proof that the device meets acceptance criteria relies entirely on the previously conducted studies for the predicate device, which presumably demonstrated acceptable clinical performance for those five analytes.

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