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The FilmArray GI Control Panel M238 is intended for use as an external positive and negative assayed quality control to monitor performance of the BIOFIRE FILMARRAY Gastrointestinal (GI) Panel and the BIOFIRE FILMARRAY Gastrointestinal (GI) Panel Mid assays on the BIOFIRE FILMARRAY systems. BIOFIRE FILMARRAY Gastrointestinal (GI) Panel and the BIOFIRE FILMARRAY Gastrointestinal (GI) Panel Mid assays qualitatively detect the following targets: Campylobacter (C. jejuni/C. coli/C. upsaliensis), Clostridium (Clostridioides) difficile toxin A/B, Plesiomonas shigelloides, Salmonella, Vibrio (V. parahaemolyticus/V. vulnificus/V. cholerae), Yersinia enterocolitica, Enteroaggregative E. coli (EAEC), Enteropathogenic E. coli (EPEC), Enterotoxigenic E. coli (ETEC) lt/st, Shiga-like toxin-producing E. coli (STEC) stx1/stx2, E. coli O157, Shigella/Enteroinvasive E. coli (EIEC), Cryptosporidium, Cyclospora cayetanensis, Entamoeba histolytica, Giardia lamblia, Adenovirus F 40/41, Astrovirus, Norovirus GI/GII, Rotavirus A, and Sapovirus. The FilmArray GI Control Panel M238 contains synthetic RNA transcripts in stabilizing solution, buffers, and preservatives. The FilmArray GI Control Panel M238 is designed for and intended to be used solely with the BIOFIRE FILMARRAY GI Panel and the BIOFIRE FILMARRAY GI Panel Mid assays. This product is not intended to replace manufacturer internal controls provided with these devices.

FilmArray GI Control Panel M238, P/N M238, is a quality control panel consisting of 2 single use, ready-to-use, liquid controls, FilmArray GI Control M239, P/N M239, and FilmArray GI Control M240, P/N M240. Each kit of FilmArray GI Control Panel M238 is comprised of 6 tubes of M239 and 6 tubes of M240. Together the 2 controls contain synthetic RNA corresponding to genome segments of all the pathogens detected by the BIOFIRE FILMARRAY Gastrointestinal (GI) Panel and BIOFIRE FILMARRAY GI Panel Mid assays, suspended in a non-infectious solution of buffers, preservatives and stabilizers.

Each liquid control of FilmArray GI Control Panel M238 is processed separately according to the BIOFIRE GI Panel and BIOFIRE GI Panel Mid manufacturer's Instructions for Use for patient samples, stool samples in Cary Blair transport media obtained from individuals with signs and/or symptoms of gastrointestinal infection.

The provided FDA 510(k) clearance letter and summary discuss the validation of the FilmArray GI Control Panel M238. This device is an assayed quality control material, not an AI/ML-driven diagnostic device. Therefore, many of the requested elements the prompt is asking for (e.g., number of experts, adjudication methods, MRMC study, training sets, human-in-the-loop performance) are not applicable to this type of device.

However, I can extract and present the relevant information regarding its acceptance criteria and the study that proves it meets those criteria, focusing on the concepts applicable to quality control materials:

Device: FilmArray® GI Control Panel M238 (M238)

This device is an external positive and negative assayed quality control used to monitor the performance of the BIOFIRE FILMARRAY Gastrointestinal (GI) Panel and the BIOFIRE FILMARRAY Gastrointestinal (GI) Panel Mid assays. It contains synthetic RNA transcripts as targets.

Acceptance Criteria and Reported Device Performance

The core acceptance criterion for a quality control material like this is its ability to consistently produce the correct expected results (either positive or negative depending on the specific control) when tested with the target assay. The study demonstrated 100% correctness across all valid tests.

Table 1: Acceptance Criteria and Reported Device Performance

Study Details Proving Acceptance Criteria are Met

1. Sample Size Used for the Test Set and Data Provenance:
* Sample Size: A total of 165 samples were tested.
* 79 samples of FilmArray GI Control M239 (positive control)
* 86 samples of FilmArray GI Control M240 (negative control)
* Data Provenance: The device was manufactured at MMQCI's facility in Saco, Maine, and tested at 2 unspecified sites. The study was prospective in nature, as it involved the creation and testing of new control lots specifically for this submission. The country of origin of the data is implicitly the USA, given the FDA filing and US company address.

2. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts:
* Not applicable in the conventional sense for a quality control material. The "ground truth" for a quality control material is its pre-defined composition, meaning it is designed to contain specific targets (for the positive control) or no targets (for the negative control). The BIOFIRE FILMARRAY GI Panel itself serves as the reference against which the control material's behavior is assessed.
* The study involved 9 operators, who presumably were trained laboratory personnel using the BIOFIRE FILMARRAY system according to its Instructions for Use. Their role was in executing the tests, not in establishing a medical "ground truth" through expert review as would be the case for image-based diagnostic AI.

3. Adjudication Method for the Test Set:
* Not applicable. The results are qualitative (Positive/Negative for specific targets, or Valid/Invalid run) and are determined by the automated output of the BIOFIRE FILMARRAY system. There is no subjective interpretation requiring adjudication among experts. The "adjudication" is purely objective: did the control material yield the expected automated result on the instrument?

4. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was done:
* No. MRMC studies are typically performed for diagnostic imaging devices where human readers interpret patient cases. This device is a quality control material for an in vitro diagnostic (IVD) assay, not a diagnostic imaging device, nor does it involve human interpretation of complex medical cases. The study demonstrated the device's ability to monitor the performance of the BIOFIRE FILMARRAY system itself.

5. If a Standalone (i.e. algorithm only without human-in-the-loop performance) was done:
* This question is more relevant to AI/ML software. In the context of this quality control material, its "standalone" performance refers to its ability to elicit the expected results from the BIOFIRE FILMARRAY system independently. The study demonstrates this functional performance, showing 100% correct results triggered by the control material when used with the instrument, which is the equivalent of "standalone" functionality for this type of product.

6. The Type of Ground Truth Used:
* Defined Composition: For quality control materials, the ground truth is the known, pre-defined composition of the control panel itself. The M239 control is designed to be positive for certain targets, and the M240 control is designed to be negative or non-reactive. The "correctness" is therefore a measure of whether the BIOFIRE FILMARRAY system, when challenged with these known controls, reports the expected results.

7. The Sample Size for the Training Set:
* Not applicable. This is a quality control material, not an AI/ML algorithm that requires a training set. The "training" for such a product implicitly involves its manufacturing and formulation process to achieve the desired composition and stability.

8. How the Ground Truth for the Training Set was Established:
* Not applicable, as there is no training set in the context of an AI/ML algorithm. For the manufacturing of the quality control material, the "ground truth" is established by the precise formulation and characterization of the synthetic RNA transcripts and other components to ensure the desired positive or negative reactivity.

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The SPOTFIRE® RSP Pos & Neg Controls kit is intended for use (as an external positive and negative assayed quality control to monitor performance of in vitro laboratory nucleic acid testing procedures for the qualitative detection of Bordetella parapertussis, Bordetella pertussis, Chlamydia pneumoniae, Mycoplasma pneumoniae, Streptococcus dysgalactiae (Group C/G Strep), Streptococcus pyogenes (Group A Strep), Adenovirus SARS-CoV-2, Coronavirus (seasonal), Human Metapneumovirus, Human Rhinovirus/Enterovirus, Influenza A Subtype H1-2009, Influenza A Subtype H3, Influenza B, Parainfluenza Virus and Respiratory Syncytial Virus using the BIOFIRE® SPOTFIRE Respiratory (R) Panel, BIOFIRE SPOTFIRE Respiratory (R) Panel Mini, BIOFIRE SPOTFIRE Respiratory/Sore Throat (R/ST) Panel and BIOFIRE SPOTFIRE Respiratory/Sore Throat (R/ST) Panel Mini on the BIOFIRE System. SPOTFIRE RSP Pos & Neg Controls is designed for and intended to be used solely with the BIOFIRE SPOTFIRE R Panel, BIOFIRE SPOTFIRE R Panel Mimi, BIOFIRE SPOTFIRE R/ST Panel, and BIOFIRE SPOTFIRE R/ST Panel Mini assays. The SPOTFIRE RSP Positive Control contains synthetic RNA transcripts in stabilizing solution, and the SPOTFIRE RSP Negative Control contains buffers and preservatives. This product is not intended to replace manufacturer internal controls provided with these devices.

Quality control materials should be used in accordance with local, state, federal regulations, and accreditation requirements.

SPOTFIRE® RSP Negative Control is intended for use (as applicable) as an external negative assayed quality control to monitor performance of in vitro laboratory nucleic acid testing procedures for the qualitative detection of Bordetella parapertussis. Bordetella pertussis. Chlamydia pneumoniae. Streptococcus dysgalactiae (Group C/G Strep), Streptococcus pyogenes (Group A Strep), Adenovirus SARS-CoV-2, Coronavirus (seasonal), Human Metapneumovirus, Human Rhinovirus, Influenza A Subtype H1-2009, Influenza A Subtype H3, Influenza B, Parainfluenza Virus and Respiratory Syncytial Virus using the BIOFIRE® SPOTFIRE Respiratory (R) Panel, BIOFIRE SPOTFIRE Respiratory (R) Panel Mini, BIOFIRE SPOTFIRE Respiratory/Sore Throat (R/ST) Panel, and BIOFIRE SPOTFIRE Respiratory/Sore Throat (R/ST) Panel Mini on the BIOFIRE System. SPOTFIRE RSP Negative Control is designed for and intended to be used solely with the BIOFIRE SPOTFIRE R Panel, BIOFIRE SPOTFIRE R Panel Mini, BIOFIRE SPOTFIRE R/ST Panel, and BIOFIRE SPOTFIRE R/ST Panel Mini assays. SPOTFIRE RSP Negative Control is comprised of a solution of buffer and preservatives that does not contain target analytes. This product is not intended to replace manufacturer internal controls provided with these devices.

Quality control materials should be used in accordance with local, state, federal regulations, and accreditation requirements.

SPOTFIRE RSP Pos & Neg Controls, P/N M425, is a quality control panel consisting of 12 readyto-use, liquid controls, 6 of SPOTFIRE RSP Positive Control (Positive Control), P/N M42638, and 6 of SPOTFIRE RSP Negative Control (Negative Control), P/N M42738, in a single kit box, and a separate kit of 6 additional SPOTFIRE RSP Negative Controls (Negative Control), P/N M42738. The separate kit of SPOTFIRE RSP Negative Control allows and encourages the end user to check for environmental contamination by testing additional negative controls. The Positive Control contains non-infectious surrogate control material; a solution of synthetic RNA transcripts in buffer, stabilizers and preservatives. The RNA in the Positive Control carries RNA segments of all the respiratory and sore throat pathogens detected by the BIOFIRE SPOTFIRE Respiratory (R) Panel, BIOFIRE SPOTFIRE Respiratory (R) Panel Mini, BIOFIRE SPOTFIRE Respiratory/Sore Throat (R/ST) Panel, and BIOFIRE SPOTFIRE Respiratory/Sore Throat (R/ST) Panel Mini assays. performed on the BIOFIRE System. SPOTFIRE RSP Pos & Neg Controls are specifically designed for and intended to be used solely with the BIOFIRE SPOTFIRE R Panel, BIOFIRE SPOTFIRE R Panel Mini, BIOFIRE SPOTFIRE R/ST Panel, and BIOFIRE SPOTFIRE R/ST Panel Mini assays on the BIOFIRE SPOTFIRE System. The Negative Control contains buffer and preservatives with no RNA. Each liquid control of SPOTFIRE RSP Pos & Neg Controls is processed separately according to the SPOTFIRE Panel assay manufacturer's Instructions for Use for patient samples (nasopharyngeal swabs or throat swabs placed in transport media) obtained from individuals with signs and symptoms of respiratory tract infection or pharyngitis. Engineering drawings, schematics, etc. are not applicable to the device (device is a reagent).

The provided text is a 510(k) premarket notification for a medical device called "SPOTFIRE® RSP Pos & Neg Controls." This document focuses on the regulatory aspects of changing an existing, cleared device (K233611) rather than presenting a detailed study proving performance against specific acceptance criteria for a new device.

Therefore, I cannot extract the information required to populate a table of acceptance criteria and reported device performance from this document, nor can I describe a study that proves the device meets specific acceptance criteria in the context of an AI/ML-driven medical device, as the device in question is an assayed quality control material for clinical microbiology assays, not an AI/ML diagnostic tool.

The document states:

• "Performance data presented in the predicate 510(k) submission (K233611) has all the required data to support the labeling change to the existing device to include the SPOTFIRE R/ST Panel Mini in the intended use for SPOTFIRE RSP Pos & Neg Controls, and the packaging change to combine Positive and Negative controls in a single kit box. No additional performance data are required as the SPOTFIRE RSP Pos & Neg Controls have not been changed, the assay consumables are identical for the SPOTFIRE R/ST Panel used to collect original performance data and the SPOTFIRE R Panel Mini. In addition, the targets reported in the SPOTFIRE R/ST Panel Mini are a subset of the SPOTFIRE R/ST Panel."

This explicitly states that no new performance study was conducted for this specific submission (K241289) because the changes were considered minor (labeling and packaging, and the new panel is a subset of an already cleared panel). The previous 510(k) (K233611) would contain the original performance data, but that information is not provided in this document.

As a result, I cannot provide details on:

1. A table of acceptance criteria and the reported device performance: Not present, as no new performance study was conducted.
2. Sample size used for the test set and data provenance: Not present.
3. Number of experts used to establish ground truth and qualifications: Not applicable/present.
4. Adjudication method for the test set: Not applicable/present.
5. Multi Reader Multi Case (MRMC) comparative effectiveness study: Not applicable, as this is a quality control material, not an AI diagnostic tool involving human readers.
6. Standalone (algorithm only) performance: Not applicable.
7. Type of ground truth used (expert consensus, pathology, outcomes data, etc.): Not applicable/present in this document.
8. Sample size for the training set: Not applicable (not an AI/ML device, and no new training/testing).
9. How the ground truth for the training set was established: Not applicable.

The document's purpose is to demonstrate substantial equivalence to an existing predicate device based on minor changes, not to present novel performance data for a new device.

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SPOTFIRE® RSP Positive Control is intended for use (as applicable) as an external positive assayed quality control to monitor performance of in vitro laboratory nucleic acid testing procedures for the qualitative detection of Bordetella parapertussis, Bordetella pertussis, Chlamydia pneumoniae, Mycoplasma pneumoniae, Streptococcus dysgalactiae (Group C/G Strep), Streptococcus pyogenes (Group A Strep), Adenovirus SARS-CoV-2, Coronavirus (seasonal), Human Metapneumovirus, Human Rhinovirus, Influenza A Subtype H1-2009, Influenza A Subtype H3, Influenza B, Parainfluenza Virus and Respiratory Syncytial Virus using the BIOFIRE® SPOTFIRE Respiratory (R) Panel, BIOFIRE SPOTFIRE Respiratory (R) Panel Mimi, and BIOFIRE SPOTFIRE Respiratory/Sore Throat (R/ST) Panel on the BIOFIRE SPOTFIRE System. SPOTFIRE RSP Positive Control is comprised of in vitro RNA transcripts and stabilizing solution and is designed for and intended to be used solely with the BIOFIRE SPOTFIRE R Panel, BIOFIRE SPOTFIRE R Panel Mini, and BIOFIRE SPOTFIRE R/ST Panel assays. This product is not intended to replace manufacturer internal controls provided with these devices.

Quality control materials should be used in accordance with local, state, federal regulations, and accreditation requirements.

SPOTFIRE® RSP Negative Control is intended for use (as applicable) as an external negative assayed quality control to monitor performance of in vitro laboratory nucleic acid testing procedures for the qualitative detection of Bordetella parapertussis, Bordetella pertussis, Chlamydia pneumoniae, Streptococcus dysgalactiae (Group C/G Strep), Streptococcus pyogenes (Group A Strep), Adenovirus SARS-CoV-2, Coronavirus (seasonal), Human Metapneumovirus, Human Rhinovirus, Influenza A Subtype H1-2009, Influenza A Subtype H3, Influenza B, Parainfluenza Virus and Respiratory Syncytial Virus using the BIOFIRE® SPOTFIRE Respiratory (R) Panel, BIOFIRE SPOTFIRE Respiratory (R) Panel Mini, and BIOFIRE SPOTFIRE Respiratory/Sore Throat (R/ST) Panel on the BIOFIRE System. SPOTFIRE RSP Negative Control is comprised of a solution that does not contain target and is designed for and intended to be used solely with the BIOFIRE SPOTFIRE R Panel, BIOFIRE SPOTFIRE R Panel Mini, and BIOFIRE SPOTFIRE R/ST Panel assays. This product is not intended to replace manufacturer internal controls provided with these devices.

SPOTFIRE RSP Pos & Neg Controls, P/N M425, is a quality control panel consisting of 2 readyto-use, liquid controls, SPOTFIRE RSP Positive Control (Positive Control), P/N M42638 and SPOTFIRE RSP Negative Control (Negative Control), P/N M42738. The Positive Control contains non-infectious surrogate control material; a solution of synthetic RNA transcripts in buffer, stabilizers and preservatives. The RNA in the Positive Control carries RNA segments of all the respiratory and sore throat pathogens detected by the BIOFIRE SPOTFIRE Respiratory (R) Panel, BIOFIRE SPOTFIRE Respiratory (R) Panel Mini, and BIOFIRE SPOTFIRE Respiratory/Sore Throat (R/ST) Panel assays, performed on the BIOFIRE System. The Negative Control contains buffer and preservatives with no RNA. Each liquid control of SPOTFIRE RSP Pos & Neg Controls is processed separately according to the SPOTFIRE Panel assay manufacturer's Instructions for Use for patient samples (nasopharyngeal swabs or throat swabs placed in transport media) obtained from individuals with signs and symptoms of respiratory tract infection or pharyngitis.

The provided text is a 510(k) Summary for a medical device called "SPOTFIRE RSP Pos & Neg Controls," which are quality control materials for molecular diagnostic assays. The submission is a change to an existing device (K230868) to include compatibility with a new panel, the "BIOFIRE SPOTFIRE Respiratory/Sore Throat (R/ST) Panel."

The document details the device's intended use, its description, and a summary of performance data collected to demonstrate that the modified device remains substantially equivalent to its predicate.

Here's the breakdown of the acceptance criteria and study information, as requested:

Acceptance Criteria and Reported Device Performance

Study Information

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

   • Total Test Results: 361 initially, with 10 invalid results that were repeated, leading to 351 valid test results used for performance analysis.
   • Data Provenance:
     • External Study: 232 test results collected from 5 near-patient clinical sites. The document does not specify the country of origin of these sites, but given the FDA submission, it's presumed to be in the USA. This was a prospective study as the sites were asked to follow specific protocols for testing controls during normal operations (e.g., training new operators, new kit shipments, new/repaired instruments).
     • Internal Study: 129 test results collected from MMQCI's facility in Saco, Maine (USA). This was also a prospective study.

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

   • This study evaluates the performance of quality control materials for in vitro laboratory nucleic acid testing. The "ground truth" here is objective: either the control produced the expected positive result (detecting the specified analytes) or the expected negative result (no target analytes detected).
   • Therefore, no human experts (like radiologists) were establishing a subjective "ground truth" diagnosis. The performance is based on whether the automated instrument correctly identifies the presence or absence of the target analytes in the control material as designed.

3. Adjudication Method for the Test Set:

   • Not applicable in the conventional sense of human expert discrepancies. The performance is measured against the pre-defined composition of the positive and negative control materials.
   • Invalid results (instrument errors, failed internal pouch controls) were re-tested according to BioFire instructions and excluded from the "Percent Correct" analysis. This acts as a form of "adjudication" for technical failures rather than diagnostic disagreement.

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

   • No, an MRMC comparative effectiveness study was not done. This study is not evaluating a diagnostic AI algorithm that assists human readers. It's evaluating the performance of quality control materials for a molecular diagnostic assay. The "users" are laboratory professionals (or non-lab professionals in CLIA waived settings) operating the BIOFIRE SPOTFIRE System. The study assessed the reproducibility of the control materials, not the improvement of human readers with AI assistance.

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

   • This is not an AI algorithm. The performance evaluation is inherently "standalone" in the sense that the control materials are processed by the BIOFIRE SPOTFIRE System, and the system's output (positive or negative detection of specific analytes) is compared against the known composition of the control. The "human-in-the-loop" would be the technician performing the test, but their role is to follow instructions, not to interpret complex images or data subjectively.

6. The Type of Ground Truth Used:

   • The ground truth is the known, manufactured composition of the control materials.
     • Positive Control: Contains synthetic RNA transcripts for all target respiratory and sore throat pathogens. The ground truth is that these specific targets should be detected by the assay.
     • Negative Control: Contains buffer and preservatives with no RNA targets. The ground truth is that no target analytes should be detected.

7. The Sample Size for the Training Set:

   • Not applicable. This device is a quality control material, not a machine learning or AI model. Therefore, there is no "training set" in the context of algorithm development. The control materials are manufactured to a specific design.

8. How the Ground Truth for the Training Set was Established:

   • Not applicable, as there is no training set for an AI/ML model. The ground truth for the control materials is inherent in their design and manufacturing process.

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The HAVAb IgG II assay is a chemiluminescent microparticle immunoassay (CMA) used for the qualitative detection of IgG antibody to hepatitis A virus (IgG anti-HAV) in human adult and pediatric (4 through 21 years) serum (collected in serum and serum separator tubes) and plasma (collected in sodium heparin, lithium heparin separator, dipotassium EDTA, and tripotassium EDTA tubes) from patients with signs and symptoms or at risk for hepatitis A on the Alinity i system.

The HAVAb IgG II assay is used to determine the immune status of individuals to hepatitis A virus (HAV) infection. Warning: This assay has not been cleared for use in screening blood, plasma, or tissue donors. This assay camot be used for the diagnosis of acute HAV infection.

Assay performance characteristics have not been established when the HAVAb IgG II assay is used in conjunction with other hepatitis assays.

The HAVAb IgG II assay is a chemiluminescent microparticle immunoassay (CMIA) used for the qualitative detection of IgG antibody to hepatitis A virus (IgG anti-HAV) in human adult and pediatric (4 through 21 years) serum (collected in serum and serum separator tubes) and plasma (collected in sodium heparin, lithium heparin separator, dipotassium EDTA, and tripotassium EDTA tubes) from patients with signs and symptoms or at risk for hepatitis A on the Alinity i system. The kit includes reagents (Microparticles, Conjugate, Assay Diluent), Calibrator, and Controls. The assay is an automated, two-step immunoassay.

Considering the provided document, the device described is an in vitro diagnostic (IVD) assay (HAVAb IgG II) for the qualitative detection of IgG antibody to hepatitis A virus (IgG anti-HAV). The FDA 510(k) summary focuses on establishing substantial equivalence to a predicate device, not on meeting specific acceptance criteria in the context of an AI/ML medical device's performance evaluation against clinical ground truth.

Therefore, many of the requested criteria (like ground truth establishment by experts, adjudication methods, multi-reader multi-case studies, and separate training/test sets with their ground truth establishment) are generally not applicable to the performance claims made for this in vitro diagnostic device in this FDA submission. The document describes analytical and clinical performance studies typical for an IVD, focusing on agreement with a predicate device and reproducibility/precision, rather than predictive performance of an AI model against a complex clinical endpoint established by human experts.

Based on the provided text, here's a breakdown of the information that is applicable and a clear indication where the requested information is not present or relevant to this type of device submission:

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

The document doesn't explicitly state "acceptance criteria" in a table format that would typically be found for an AI/ML model for diagnostic imaging (e.g., target sensitivity/specificity values). Instead, it presents performance data for comparison to a predicate device and for reproducibility. The implicit "acceptance criterion" for a 510(k) is demonstrating "substantial equivalence" to a legally marketed predicate device.

However, we can infer some performance metrics presented as evidence of equivalence:

2. Sample sizes used for the test set and the data provenance

• Clinical Performance Test Set (Agreement with Predicate):

  • Individuals at Increased Risk of HAV Infection: n=250
  • Individuals with Signs and Symptoms of Hepatitis Infection: n=499
  • Pediatric Population: n=105
  • Total for Agreement Study: 250 + 499 + 105 = 854 specimens.
  • Data Provenance: Prospective multi-center study.
    • Increased Risk of HAV: collected in California, Colorado, Florida, Illinois, Massachusetts, North Carolina, and Texas.
    • Signs and Symptoms of Hepatitis: collected in California, Colorado, Florida, Illinois, Massachusetts, and Texas.
    • Pediatric Population: collected in the US (California and Massachusetts) and Belgium.

• Precision/Reproducibility Test Sets:

  • Within-Laboratory Precision: n=80 per sample/control for a representative combination (tested over 20 days, 2 replicates/day). Total tested for this study was 4 reagent/calibrator/instrument combinations.
  • System Reproducibility: n=360 per sample/control (tested at 3 sites, with 4 replicates/run, 2 runs/day, 5 days).

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

• Not applicable / Not stated. For this IVD device, the "ground truth" for the clinical performance study was the result produced by the legally marketed predicate device (ARCHITECT HAVAB-G). This is a common practice for 510(k) submissions for IVDs. There were no human experts adjudicating results for the purpose of establishing a "ground truth" beyond what the predicate device determined.

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

• Not applicable. As the ground truth was the predicate device's result, no human adjudication method (like 2+1, 3+1) was used or described.

5. If a multi reader multi case (MRMC) comparative effectiveness study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance

• Not applicable. This is an in vitro diagnostic assay, not an imaging AI device intended to assist human readers. Therefore, an MRMC study and evaluation of human reader improvement with AI assistance were not performed.

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

• Yes, in spirit. The device (HAVAb IgG II assay) functions as a standalone test; it's an automated immunoassay that generates a qualitative result (Reactive or Nonreactive) without human interpretation in the loop influencing the output beyond sample collection and instrument operation. Its performance was assessed directly against the predicate device's results.

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

• The "ground truth" for the clinical performance comparison was the results from a legally marketed predicate device (ARCHITECT HAVAB-G assay). In essence, the performance of the new device was compared to the established performance of the predicate. This is a common form of "truth" in demonstrating substantial equivalence for IVDs.

8. The sample size for the training set

• Not explicitly stated in terms of a "training set" for model development. This is an immunoassay, not an AI/ML model where a distinct training dataset size is typically reported. The document describes analytical verification and clinical performance studies, not model training.

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

• Not applicable. As this is not an AI/ML device in the sense of a machine learning model requiring a training set with a ground truth established by experts for supervised learning, this information is not provided. The development process for an immunoassay does not involve "training data" in the same way an AI/ML model does.

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MDx-Chex™ for BC-GP is intended for use as an external positive assayed control to monitor the performance of the qualitative detection of Gram-positive bacteria and associated antimicrobial resistance genes, by the Luminex VERIGENE® Gram-Positive Blood Culture Nucleic Acid Test (BC-GP) on Luminex VERIGENE® systems. The MDx-Chex™ for BC-GP Positive and Negative Controls are composed of a buffered solution with stabilized erythrocytes and leukocytes in a matrix of blood culture media components. Positive bacteria: Staphylococcus aureus, Staphylococus epidermidis, Staphylococcus lugdunensis, Streptococcus agalactiae, Streptococcus pneumoniae, Streptococus pyogenes, Enterococcus faecium, Streptococus faecium, Streptococus anginosus group; Species: Staphylococcus spp., Streptococcus spp.; antimicrobial resistance genes: mecA, vanA and vanB. Negative Control: buffered solution only. This product is not intended to replace manufacturer controls provided with the device.

MDx-Chex™ for BC-GP is a quality control kit consisting of positive and negative controls for the Luminex VERIGENE® Gram-Positive Blood Culture Test (BC-GP). The MDx-Chex™ for BC-GP Positive Control is positive for pathogens and resistance mechanisms in the VERIGENE BC-GP test (See Table 1). The MDx-Chex™ for BC-GP Negative Control is negative for pathogens and resistance mechanisms in the VERIGENE BC-GP test. Each control mix also controls for blood and blood culture media components that have been identified is inhibitors to DNA hybridization assays, namely hemoglobin, leukocyte DNA, and anticoagulants.

The MDx-Chex™ for BC-GP quality control kit contains stabilized blood components, blood culture media components, and inactivated, intact microorganisms resulting in a full-process, cellular-based control for the Luminex VERIGENE BC-GP panel.

Here's a breakdown of the acceptance criteria and the study used to prove the device meets these criteria, based on the provided text:

Device: MDx-Chex™ for BC-GP (Assayed Quality Control Material For Clinical Microbiology Assays)

Intended Use: To monitor the performance of qualitative detection of Gram-positive bacteria and associated antimicrobial resistance genes by the Luminex VERIGENE® Gram-Positive Blood Culture Nucleic Acid Test (BC-GP) on Luminex VERIGENE® systems.

1. Table of Acceptance Criteria and Reported Device Performance

The acceptance criterion for all performance studies is ≥ 90% agreement with expected results.

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

• Multi-Site Precision (Reproducibility):
  • Sample Size: 30 positive control samples and 30 negative control samples per lot (for each site, making a total of 90 positive and 90 negative samples across 3 sites for 1 lot, and 180 total runs per control type for all lots). The study used 3 lots, so effectively 30 positive and 30 negative tests per lot across 3 sites.
  • Provenanc: Not explicitly stated, but implies a prospective study conducted at 3 different sites as part of device validation.
• Single-Site Precision (Repeatability):
  • Sample Size: 20 samples per control type (positive and negative control tubes), 40 samples per MDx-Chex™ for BC-GP lot. Across 3 lots, this accumulated to 120 runs (20 runs per control type per lot across 3 lots).
  • Provenance: Not explicitly stated, but implies a prospective study conducted at a single site as part of device validation.
• Lot-to-Lot Reproducibility:
  • Sample Size: For the Lot-to-lot study, data from 10 positive and 10 negative control tubes per lot (30 data points per control type across 3 lots, totaling 60 data points). For the within-run precision, 10 tests for each positive and negative control tube from one lot (total of 20 tests).
  • Provenance: Not explicitly stated, but implies a prospective study.
• Closed-Vial Stability and Shipping Stability:
  • Sample Size: 20 positive and 20 negative control samples per MDx-Chex lot, collected at different data collection timepoints and stored at room (25°C) and refrigerated (2°C) temperatures. With 3 lots, this amounts to 60 positive and 60 negative total samples tested for each storage condition and time point. For shipping stability, one lot with 20 samples per control type for each simulated shipping profile.
  • Provenance: Not explicitly stated, but implies a prospective study.
• Matrix Effect:
  • Sample Size: Simulated positive MDx-Chex™ for BC-GP matrix and simulated positive clinical sample were tested in triplicate (3 samples each). Similarly, non-spiked simulated samples (negative controls) were tested in triplicate.
  • Provenance: Not explicitly stated, but implies a prospective study.

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

This device is an assayed quality control material for in vitro diagnostic tests. The ground truth (i.e., whether a control is 'positive' or 'negative' for specific pathogens/resistance genes) is inherent to the control material's design and formulation, not established by human experts interpreting results. The controls contain "inactivated, intact microorganisms" and specific resistance genes, and are designed to elicit a known positive or negative result on the target diagnostic system.

4. Adjudication Method for the Test Set

Adjudication methods like "2+1" or "3+1" are typically used for studies where human interpretation or consensus is required to establish ground truth (e.g., image interpretation). For an in vitro diagnostic quality control material like MDx-Chex™ for BC-GP, the "ground truth" of what the control should detect is pre-defined by its composition. There is no human adjudication process described or expected. The results from the Luminex VERIGENE® system are compared directly to the expected outcome of the quality control material.

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 relevant for diagnostic devices that involve human interpretation (e.g., radiologists reading images) and assessing how AI assistance might improve human performance. MDx-Chex™ for BC-GP is a quality control material for an automated molecular diagnostic test (Luminex VERIGENE® BC-GP) and does not involve human interpretation in the same way. The studies focus on the performance and stability of the control material itself.

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

Yes, implicitly, the studies evaluate the "standalone" performance of the MDx-Chex™ controls when processed by the Luminex VERIGENE® System. Since the device is a quality control material, its "performance" is its ability to consistently produce the expected positive or negative results on the target instrument. The data presented demonstrates the consistency of these expected results. There's no "human-in-the-loop" component for the performance of the control material, other than operators performing the assay.

7. The Type of Ground Truth Used

The ground truth is pre-defined by the engineered composition of the quality control material.

• For the Positive Control, the ground truth is "Detected" for specific Gram-positive bacteria (e.g., Staphylococcus aureus, Enterococcus faecalis, Streptococcus pneumoniae) and antimicrobial resistance genes (mecA, vanA, vanB) that are intentionally included in the control.
• For the Negative Control, the ground truth is "Not Detected" because it is a buffered solution only, without the target microorganisms or resistance genes.

8. The Sample Size for the Training Set

Not applicable. This device is a quality control material, not an AI/machine learning algorithm that requires a training set. Its purpose is to monitor the performance of another diagnostic assay (Luminex VERIGENE® BC-GP), not to make diagnostic predictions itself.

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

Not applicable, as there is no training set for this device.

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MDx-Chex™ for BC-GN is intended for use as an external positive and negative assayed control to monitor the performance of the qualitative detection of Gram-Negative bacteria and associated antimicrobial resistance genes, by the Luminex VERIGENE® Gram-Negative Blood Culture Nucleic Acid Test (BC-GN) on Luminex VERIGENE® systems. The MDx-Chex™ for BC-GN Positive and Negative Controls are composed of a buffered solution with stabilized erythrocytes and leukocytes in a matrix of blood culture media components. Positive Control: Gram-negative bacteria: Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca, Pseudomonas aeruginosa, Species: Acinetobacter spe., Citrobacter spp., Enterobacter spp., Proteus spp.; antimicrobial resistance genes: CTX-M, IMP, KPC, NDM, OXA and VIM. Negative Control: buffered solution only. This product is not intended to replace manufacturer controls provided with the device.

MDx-Chex™ for BC-GN is a quality control kit consisting of positive and negative controls for the Luminex VERIGENE® Gram-Negative Blood Culture Test (BC-GN). The MDx-Chex™ for BC-GN Positive Control is positive for pathogens and resistance mechanisms in the VERIGENE BC-GN test (See Table 1). The MDx-Chex™ for BC-GN Negative Control is negative for pathogens and resistance mechanisms in the VERIGENE BC-GN test. Each control mix also controls for blood and blood culture media components that have been identified is inhibitors to DNA hybridization assays, namely hemoglobin, leukocyte DNA, and anticoagulants.

The MDx-Chex™ for BC-GN quality control kit contains stabilized blood components, blood culture media components, and inactivated, intact microorganisms resulting in a full-process, cellular-based control for the Luminex VERIGENE BC-GN panel. Use of full-process cellular controls are necessary to evaluate the entire analytical process, including sample lysis, nucleic acid isolation, DNA hybridization detection, and analysis, as well as the impact of inhibitors present in blood culture samples and preanalytical variables. Routine use of full process quality controls can help identify variations in the test system that can lead to incorrect results.

The provided document describes the performance of the MDx-Chex™ for BC-GN device, a quality control material, rather than an AI/ML medical device for diagnosis or prediction. Therefore, many of the requested categories (e.g., number of experts, adjudication method, MRMC comparative effectiveness, standalone performance, training set details) are not applicable to this type of device and study.

However, I can extract the acceptance criteria and reported device performance from the provided text for the relevant studies.

Acceptance Criteria and Device Performance

The general acceptance criterion for all studies (Multi-Site Precision, Single-Site Precision, Lot-to-Lot Reproducibility, Closed-Vial Stability, and Shipping Stability) was ≥ 90% agreement with expected results. For Matrix Effect studies, the acceptance criteria was also ≥ 90% agreement for positive detection of analyte for positive controls and ≥ 90% agreement for negative detection of analyte for negative controls.

1. Table of Acceptance Criteria and the Reported Device Performance

2. Sample sizes used for the test set and the data provenance

• Multi-Site Precision:

  • Sample Size: 10 positive control samples and 10 negative control samples for each of 3 MDx-Chex™ for BC-GN lots, tested across 3 sites, for a total of 30 samples per control type per lot. This resulted in 90 runs per control type (positive/negative) and 180 total runs for data analysis.
  • Data Provenance: Not explicitly stated, but implies a prospective study design conducted by the manufacturer (Streck) for regulatory submission.

• Single-Site Precision (Repeatability):

  • Sample Size: 20 samples per control type (positive and negative) for each of 3 MDx-Chex™ for BC-GN lots, tested over 20 days. This resulted in 120 runs (20 runs per control type per lot) for data analysis.
  • Data Provenance: Not explicitly stated, but implies a prospective study design conducted by the manufacturer (Streck).

• Lot-to-Lot Reproducibility:

  • Sample Size: 10 positive and 10 negative control tubes per MDx-Chex™ for BC-GN lot (3 lots), resulting in 30 data points per control type (60 total data points).
  • Data Provenance: Not explicitly stated, but implies a prospective study design conducted by the manufacturer (Streck).

• Within-Run Precision:

  • Sample Size: 10 tests for each positive and negative control tube from one MDx-Chex™ for BC-GN lot (total of 20 tests).
  • Data Provenance: This data was sourced from the Day 60 (2C) closed-vial stability data.

• Closed-Vial Stability and Shipping Stability:

  • Sample Size: 20 positive and 20 negative control samples per MDx-Chex™ for BC-GN lot (3 lots), collected at different timepoints and stored at different temperatures. For shipping: one lot (RPL #22355) with 20 samples per control type for each simulated shipping profile.
  • Data Provenance: Not explicitly stated, but implies a prospective study design conducted by the manufacturer (Streck).

• Matrix Effect:

  • Sample Size: Simulated positive MDx-Chex™ for BC-GN matrix (triplicate), simulated positive clinical sample (triplicate), simulated negative MDx-Chex™ for BC-GN matrix (triplicate), simulated negative clinical sample (triplicate). Total of 12 tests.
  • Data Provenance: Not explicitly stated, but implies a prospective study design conducted by the manufacturer (Streck).

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

Not applicable. This device is a quality control material for an in vitro diagnostic test. The "ground truth" is defined by the expected performance of the control material (i.e., whether it should be detected as positive or negative for specific pathogens/genes by the Luminex VERIGENE® BC-GN system). This "ground truth" is inherent to the control material's formulation and its intended reactivity with the target diagnostic system, not established by human experts.

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

Not applicable. As a quality control material, the "ground truth" is binary (positive/negative for specific targets) and is determined by the composition of the control and the design of the diagnostic test it monitors. There is no human adjudication process involved.

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 not an AI/ML diagnostic device, nor does it involve human readers or cases. It is a quality control material for an automated molecular diagnostic test.

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

The performance detailed is that of the quality control material when used "standalone" with the Luminex VERIGENE® Gram-Negative Blood Culture Nucleic Acid Test (BC-GN) on Luminex VERIGENE® systems. The "algorithm" in this context refers to the Luminex VERIGENE® system itself, and the studies assess how well the control material performs within that system as expected. The control itself does not have an "algorithm."

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

The "ground truth" for these studies is the expected reactivity of the quality control material with the Luminex VERIGENE® BC-GN system.

• Positive Controls: Expected to be "Detected" for specific Gram-negative bacteria and antimicrobial resistance genes.
• Negative Controls: Expected to be "Not Detected" (buffered solution only).
  This ground truth is based on the known composition of the MDx-Chex™ for BC-GN control material.

8. The sample size for the training set

Not applicable. This device is a quality control material, not an AI/ML model that requires training data.

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

Not applicable. See point 8.

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SPOTFIRE® RSP Positive Control is intended for use (as applicable) as an external positive assayed quality control to monitor performance of in vitro laboratory nucleic acid testing procedures for the qualitative detection of Bordetella parapertussis, Bordetella pertussis, Chlamydia pneumoniae, Adenovirus, Adenovirus, seasonal Coronavirus, Coronavirus SARS-CoV-2, Human Metapneumovirus, Human Rhinovirus, Influenza A Subtype H1-2009, Influenza A Subtype H3, Influenza B, Parainfluenza Virus and Respiratory Syncytial Virus using the BIOFIRE® SPOTFIRE® Respiratory (R) Panel (SPOTFIRE® R Panel) and BIOFIRE® Respiratory (R) Panel Mini (SPOTFIRE® R Panel Mini) assays performed on the BIOFIRE® System. SPOTFIRE® RSP Positive Control is comprised of in vitro RNA transcripts and stabilizing solution and is designed for and intended to be used solely with the SPOTFIRE R Panel and the SPOTFIRE R Panel Mini assays. This product is not intended to replace manufacturer internal controls provided with the device.

Quality control materials should be used in accordance with local, state, federal regulations, and accreditation requirements.

SPOTFIRE® RSP Negative Control is intended for use (as applicable) as an external negative assayed quality control to monitor performance of in vitro laboratory nucleic acid testing procedures for the qualitative detection of Bordetella parapertussis, Bordetella pertussis, Chlamydia pneumoniae, Adenovirus, Adenovirus, seasonal Coronavirus, Coronavirus SARS-CoV-2, Human Metapneumovirus, Human Rhinovirus, Influenza A Subtype H1-2009, Influenza A Subtype H3, Influenza B, Parainfluenza Virus and Respiratory Syncytial Virus using the BIOFIRE® SPOTFIRE® Respiratory (R) Panel (SPOTFIRE® R Panel) and BIOFIRE® Respiratory (R) Panel Mini (SPOTFIRE® R Panel Mini) assays performed on the BIOFIRE® System. SPOTFIRE® RSP Negative Control is comprised of a solution that does not contain target analytes and is designed for and intended to be used solely with the SPOTFIRE R Panel and SPOTFIRE R Panel Mini assays. This product is not intended to replace manufacturer internal controls provided with the device.

Quality control materials should be used in accordance with local, state, federal regulations, and accreditation requirements.

SPOTFIRE RSP Pos & Neg Controls, P/N M425, is a quality control panel consisting of 2 separate kits of ready-to-use, liquid controls, SPOTFIRE RSP Positive Control (Positive Control), P/N M42638 and SPOTFIRE RSP Negative Control (Negative Control), P/N M42738. The Positive Control contains non-infectious surrogate control material; a solution of synthetic RNA transcripts in buffer, stabilizers and preservatives. The RNA in the Positive Control carries RNA segments of all the respiratory pathogens detected by the SPOTFIRE R Panel (Table 1) and SPOTFIRE R Panel Mini (Table 2) on the SPOTFIRE System and is specifically designed for and intended to be used solely with the SPOTFIRE R Panel and SPOTFIRE R Panel Mini assays on the SPOTFIRE System. The Negative Control contains buffer and preservatives with no RNA. Each liquid control of SPOTFIRE RSP Pos & Neg Controls, P/N M425, is processed separately according to the SPOTFIRE R Panel and SPOTFIRE R Panel Mini assay manufacturer's Instructions for Use for Quality Control testing.

This document describes a 510(k) premarket notification for a change to an existing device, the SPOTFIRE® RSP Pos & Neg Controls. The change specifically involves including the BIOFIRE® SPOTFIRE® Respiratory (R) Panel Mini (SPOTFIRE R Panel Mini) in the device's intended use. As such, the presented information focuses on demonstrating substantial equivalence rather than a detailed de novo device performance study.

Based on the provided text, the device in question is an "Assayed Quality Control Material For Clinical Microbiology Assays". The performance data presented in the 510(k) submission (K221253) for the original device is deemed sufficient to support the change, meaning no new performance data specific to this submission (K230868) was generated.

Here's a breakdown of the requested information based on the provided text:

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

The document explicitly states: "No additional performance data are required as the SPOTFIRE RSP Pos & Neg Controls have not been changed, the assay consumables are identical for the SPOTFIRE R Panel used to collect original performance data and the SPOTFIRE R Panel Mini added to the intended use of the device. In addition, the targets reported in the SPOTFIRE R Panel Mini are a subset of the SPOTFIRE R Panel."

This indicates that the performance of the control material (SPOTFIRE® RSP Pos & Neg Controls) with the SPOTFIRE R Panel Mini is expected to be consistent with its performance on the broader SPOTFIRE R Panel, for which performance data was previously submitted and accepted under K221253.

Therefore, the table of acceptance criteria and reported device performance from the original K221253 submission would be relevant, but those details are not provided in this document.

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

No new test set was used for this specific 510(k) submission (K230868). The submission relies on performance data from the previous submission (K221253). The document does not provide details of the sample size or data provenance from K221253.

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 document. As this submission is for a quality control material and not an AI/ML diagnostic algorithm relying on expert interpretation of images, the concept of "experts establishing ground truth" in the same manner as for image-based diagnostics is not directly applicable. For a quality control material, the ground truth is typically established by the known composition of the control material itself (e.g., presence or absence of specific RNA transcripts).

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

Not applicable, as no new test set requiring adjudication of interpretations was presented in this submission.

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 quality control material, not an AI/ML diagnostic tool, and therefore MRMC studies are not relevant.

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

Not applicable. This device operates as a control for an in vitro diagnostic test, not as a standalone algorithm.

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

For a quality control material like the SPOTFIRE® RSP Pos & Neg Controls, the ground truth is the defined composition of the control material itself.

• Positive Control: Contains "in vitro RNA transcripts" of the target pathogens. So, the ground truth for the positive control is the presence of these specific RNA transcripts.
• Negative Control: Comprised of a "solution that does not contain target analytes." So, the ground truth for the negative control is the absence of the target analytes.

8. The sample size for the training set:

Not applicable. This device is a quality control material, not an AI/ML algorithm that requires a training set.

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

Not applicable, as there is no training set for this type of device.

Summary of Device Acceptance & Study Information (Based on the Provided Text):

The acceptance of K230868 is based on demonstrating substantial equivalence to the previously cleared predicate device (K221253). The core argument for acceptance is that:

• The SPOTFIRE® RSP Pos & Neg Controls have not been physically changed.
• The assay consumables for the original SPOTFIRE R Panel and the newly included SPOTFIRE R Panel Mini are identical.
• The targets detected by the SPOTFIRE R Panel Mini are a subset of those included in the SPOTFIRE R Panel, which was already covered by the previous clearance.

Therefore, the performance data previously submitted for K221253 is considered sufficient and no new performance studies specific to the addition of the SPOTFIRE R Panel Mini were required for this submission. The "study that proves the device meets the acceptance criteria" refers to the previously conducted and accepted studies for K221253, the details of which are not included in this document.

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The BioFire® Global Fever Special Pathogens Panel is a qualitative, mucleic acid-based test intended for use with BioFire® FilmArray® 2.0 and BioFire® FilmArray® Torch Systems. The BioFire Global Fever Special Pathogens Panel is for the simultaneous qualitative detection and identification of multiple bacterial, viral, and protozoan nucleic acids directly from EDTA whole collected from individuals with signs and or symptoms of acute febrile illness and known or suspected exposure to the target pathogens described below.

Pathogens identified:
Chikungunya virus Dengue virus (serotypes 1, 2, 3 and 4) Leishmania spp. that cause visceral leishmaniasis (e.g., L. donovani and L. infantum) Leptospira spp. Plasmodium spp. (including species differentiation of Plasmodium falciparum and Plasmodium vivax/ovale) West Nile virus

Pathogens presumptively identified:
Bacillus anthracis Crimean-Congo hemorrhagic fever virus Ebolavirus spp. Francisella tularensis Lassa virus Marburgvirus Yellow fever virus Yersinia pestis

Pathogens for which the panel provides presumptive identification results resting and confirmation procedures in consultation with the appropriate public health authorities for whom reports may be necessary.

Positive results do not rule out co-infections with pathogens not included on the BioFire Global Fever Special Pathogens Panel. Not all pathogens that cause acute febrile illness are detected by this test, and nectude infection with the pathogens targeted by the device and should not be used as the sole basis for diagnosis, treatment, or other patient management decisions.

Evaluation for more common causes of acute illness (e.g., infections of the upper and lower respiratory tract or gastroenteritis, as well as non-infectious causes) should be considered prith this panel. 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 Global Fever Special Pathogens Panel as some pathogens are more common in certain geographical locations. Results are meant to be used in conjunction with other clinical, epidemiologic, and laboratory data, in accordance with the guided by the relevant public health authorities.

The BioFire Global Fever Special Pathogens Panel is indicatories having appropriate biosafety equipment, personal protective equipment (PPE), contamment facilities and persomel trained in the safe handling of diagnostic clinical specimens potentially containing any of the pathogens detected by this panel.

The BioFire Global Fever Special Pathogens Panel is indicated for use in laboratories that follow public health guidelines that address appropriate biosafety conditions, interpretation of test results, and coordination of findings with public health authorities.

For In Vitro Diagnostic Use.

The BioFire® Global Fever Special Pathogens Panel is a multiplexed nucleic acid-based test designed to be used with BioFire® FilmArray® Systems (BioFire® FilmArray® 2.0 or BioFire® FilmArray® Torch). The BioFire Global Fever Special Pathogens Panel pouch contains freezedried reagents to perform nucleic acid purification and nested, multiplexed polymerase chain reaction (PCR) with DNA melt analysis. The BioFire Global Fever Special Pathogens Panel conducts tests for the identification of bacterial, viral, and protozoan pathogens from whole blood specimens collected in EDTA tubes (Table 1). Results from the BioFire Global Fever Special Pathogens Panel are available in about 1 hour.

Here's a breakdown of the acceptance criteria and study information for the BioFire Global Fever Special Pathogens Panel:

1. Table of Acceptance Criteria and Reported Device Performance

The application does not explicitly state "acceptance criteria" for PPA and NPA. However, it presents the clinical performance results in a way that suggests these are the key metrics for evaluating agreement with comparator methods. The "Expected percent agreement was >95%" in the reproducibility study might be inferred as a general target for performance. For this table, I'll use the Reported Clinical Performance Summary (Tables 4, 5, 6) as the "Reported Device Performance" against an implied high standard of agreement.

Note on "Acceptance Criteria": The document provides performance results but doesn't explicitly state quantitative acceptance criteria (e.g., "PPA must be >95%"). However, the high percentages and confidence intervals presented imply that high sensitivity and specificity are expected for proper function. The "Reproducibility" section mentions ">95%", which can serve as a proxy for the general expectation of performance accuracy.

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

• Prospective Clinical Study Test Set:
  • Sample Size: 2139 prospectively collected whole blood specimens.
  • Data Provenance: The specimens were collected between March 2018 and March 2021 from 11 undisclosed sites. The country of origin is not explicitly stated, but the mention of "CDC Yellow Book" in the "Indications for Use" suggests a relevance to North American (US) context, although the pathogens detected indicate global relevance. The data is prospective.
• Archived Specimen Study Test Set:
  • Sample Size: 416 archived specimens.
  • Data Provenance: The specimens were collected from undisclosed sites (Site 01: 199, Site 02: 82, Site 03: 135). The country of origin is not explicitly stated. The data is retrospective.
• Contrived Specimen Study Test Set:
  • Sample Size: 50 replicates for each analyte for which archived specimens were unavailable or insufficient. This resulted in varying total number of specimens tested per analyte (e.g., CCHF virus and Marburgvirus sp. had 100 replicates, others had 50).
  • Data Provenance: Contrived specimens were prepared using residual human whole blood. This is a laboratory-based study.

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 or qualifications of experts used to establish the ground truth for the test set. Ground truth was established using "plate-based PCR comparator methods" and "additional PCR" for discrepant results. For archived specimens, they had "known analyte content" or "high likelihood of containing a given analyte." For contrived specimens, the "known composition of the contrived specimen" was the ground truth.

4. Adjudication method for the test set

The document describes "discrepancy testing" for samples where the BioFire Global Fever Special Pathogens Panel results differed from the initial comparator method results. For example:

• For Chikungunya virus, "Evidence of Chikungunya virus was found in 2/2 FP specimens by additional PCR."
• For Dengue virus, "15/17 FN specimens were positive upon BioFire Global Fever Special Pathogens Panel retest and by additional PCR, two were positive Global Fever Special Pathogens Panel retest, and eight were detected only by additional PCR."
• For Leptospira spp., "Evidence of Leptospira spp. was found in 1/1 FN specimens by BioFire Global Fever Special Pathogens Panel retest and by additional PCR, and in 3/4 FP specimens by additional PCR."
• For Plasmodium spp., similar retesting by the BioFire panel and "additional PCR" or "species-level comparator assay" was used.

This indicates an adjudication method that involves retesting with the device and/or additional PCR/comparator methods for discrepant results, rather than explicitly stating an "X+Y" consensus model among human experts.

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

No, a multi-reader multi-case (MRMC) comparative effectiveness study was not done. This device is a diagnostic assay (nucleic acid-based test), not an AI-assisted interpretation tool for human readers. Therefore, the concept of "human readers improve with AI vs without AI assistance" does not apply to this submission.

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

Yes, the performance studies (clinical, archived, contrived) evaluate the BioFire Global Fever Special Pathogens Panel as a standalone device (algorithm only). The device provides automated test interpretation and report generation, and the "user cannot access raw data" (Table 2). This means the performance metrics (PPA, NPA) reflect the algorithm's detection capabilities without human intervention in the interpretation process.

7. The type of ground truth used

The ground truth for the test sets was primarily established by:

• Comparator methods (e.g., plate-based PCR/additional PCR): For both prospective clinical and archived specimens.
• Known composition: For contrived specimens, where the analytes were intentionally spiked into the samples.
• Discrepancy testing: For cases where the device result and initial comparator result differed, further testing (usually additional PCR) was performed to resolve the discrepancy and establish the final ground truth.

8. The sample size for the training set

The document does not specify the sample size for a training set. The BioFire Global Fever Special Pathogens Panel is a diagnostic assay, and while its development would involve internal validation and optimization, the provided performance data relates to its analytical and clinical performance after development, rather than the data used for machine learning model training.

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

Since a "training set" in the context of the requested information (e.g., for an AI model) is not explicitly mentioned or relevant to this type of device submission, the document does not describe how ground truth for a training set was established. The performance studies presented are for the finished device's evaluation against established laboratory methods.

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SPOTFIRE® RSP Positive Control is intended for use as an external positive assayed quality control to monitor performance of in vitro laboratory nucleic acid testing procedures for the qualitative detection of Bordetella parapertussis, Bordetella pertussis, Chlamydia pneumoniae, Mycoplasma pneumoniae, Adenovirus, seasonal Coronavirus, Coronavirus SARS-CoV-2, Human Metapneumovirus, Human Rhinovirus, Influenza A Subtype H1-2009, Influenza A Subtype H3, Influenza B, Parainfluenza Virus and Respiratory Syncytial Virus using the BIOFIRE® SPOTFIRE® Respiratory (R) Panel performed on the BIOFIRE® SPOTFIRE® System. SPOTFIRE RSP Positive Control is comprised of in vitro RNA transcripts and stabilizing solution and is designed for and intended to be used solely with the BIOFIRE SPOTFIRE R Panel. This product is not intended to replace manufacturer internal controls provided with the device.

SPOTFIRE® RSP Negative Control is intended for use as an external negative assayed quality control to monitor performance of in vitro laboratory nucleic acid testing procedures for the qualitative detection of Bordetella parapertussis, Bordetella pertussis, Chlamydia pneumoniae, Mycoplasma pneumoniae, Adenovirus, seasonal Coronavirus, Coronavirus SARS-CoV-2, Human Metapneumovirus, Human Rhinovirus, Influenza A Subtype H1-2009, Influenza A Subtype H3, Influenza B, Parainfluenza Virus and Respiratory Syncytial Virus using the BIOFIRE® SPOTFIRE® Respiratory (R) Panel performed on the BIOFIRE® SPOTFIRE® System. SPOTFIRE RSP Negative Control is comprised of a solution that does not contain target analytes and is designed for and intended to be used solely with the BIOFIRE SPOTFIRE R Panel. This product is not intended to replace manufacturer internal controls provided with the device.

SPOTFIRE® RSP Pos & Neg Controls, P/N M425, is a quality control panel consisting of 2 separate kits of ready-to-use, liquid controls, SPOTFIRE® RSP Positive Control (Positive Control), P/N M42638 and SPOTFIRE® RSP Negative Control (Negative Control), P/N M42738. The Positive Control contains non-infectious surrogate control material; a solution of synthetic RNA transcripts in buffer, stabilizers and preservatives. The RNA in the Positive Control carries RNA segments of all the respiratory pathogens detected by the BIOFIRE® SPOTFIRE® Respiratory (R) Panel on the BIOFIRE® SPOTFIRE® System (see Table 1 below) and is specifically designed for and intended to be used solely with the SPOTFIRE R Panel assay on the SPOTFIRE System. The Negative Control contains buffer and preservatives with no RNA. Each liquid control of SPOTFIRE® RSP Pos & Neg Controls, P/N M425, is processed separately according to the SPOTFIRE R Panel assay manufacturer's Instructions for Use for Quality Control testing.

The provided text describes the acceptance criteria and the study that proves the device (SPOTFIRE® RSP Pos & Neg Controls) meets those criteria. The device being reviewed is a quality control material for clinical microbiology assays, not an AI/ML-enabled diagnostic device. Therefore, many of the requested categories pertaining to AI/ML device studies (e.g., number of experts for ground truth, adjudication methods, MRMC studies, effect size of human reader improvement with AI, standalone performance, training set details) are not applicable to this submission.

However, I can extract the relevant information regarding the acceptance criteria and the performance study for this quality control material.

Here's the information based on the provided text, focusing on what is applicable to the described device and study:

1. Table of Acceptance Criteria and Reported Device Performance

The acceptance criteria are not explicitly stated as numerical thresholds (e.g., "sensitivity must be > 90%"). Instead, the document refers to "predetermined criteria" for reproducibility that were met. The reported performance is an "overall correct result rate."

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

• Total Test Results: 361 initially, leading to 351 valid test results after repeating invalid ones.
• External Performance Study (Test Set): 232 initially, leading to 225 valid controls after repeating invalid ones.
  • Data Provenance: Prospective, collected from 5 near-patient clinical sites across the US (presumably, given the context of FDA submission, though not explicitly stated but implied by "near-patient clinical sites" in the context of an FDA filing for a US company).
• Internal Study (Test Set): 129 initially, leading to 126 valid results after repeating invalid ones.
  • Data Provenance: Prospective, conducted at MMQCI facility in Saco, Maine, USA.

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

• Not Applicable. This is a quality control material where the "ground truth" is inherent to the control material itself (i.e., whether it should be positive for specific analytes or negative for all analytes). The "correctness" of the result is determined by its agreement with the expected outcome for that control. The study evaluates the reproducibility and performance of the control and the assay system, not a diagnostic decision requiring expert consensus.

4. Adjudication Method for the Test Set

• Not Applicable. As this is a quality control material, the "ground truth" for each control (whether it should yield a positive or negative result) is predefined by its composition. There is no human adjudication process for categorizing results as "correct" or "incorrect" beyond comparing them to the expected outcome based on the control's design. Invalid results were repeated as per BioFire instructions.

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 not an AI/ML-enabled diagnostic device. No human readers, AI assistance, or comparative effectiveness studies of this nature were performed.

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

• Not Applicable. This is a physical quality control material used with an in-vitro diagnostic system (BIOFIRE® SPOTFIRE® System). Its performance is evaluated within that system, not as a standalone algorithm.

7. The Type of Ground Truth Used

• Defined Composition: The ground truth for the SPOTFIRE® RSP Positive Control is the presence of synthetic RNA transcripts corresponding to specific respiratory pathogens, manufactured to be detected by the BIOFIRE® SPOTFIRE® Respiratory (R) Panel.
• Defined Absence: The ground truth for the SPOTFIRE® RSP Negative Control is the absence of target analytes, designed to yield a negative result.
• The "correct" result for each control is based on its predetermined design and expected performance with the intended assay.

8. The Sample Size for the Training Set

• Not Applicable. As this is a quality control material and not an AI/ML model, there is no "training set." The study described evaluates the performance and reproducibility of the manufactured control materials within their intended use.

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

• Not Applicable. See point 8.

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The BioFire® Global Fever Panel is a qualitative, multiplexed, nucleic acid-based in vitro diagnostic test intended for use with BioFire® FilmArray® 2.0 and BioFire® FilmArray® Torch Systems. The BioFire Global Fever Panel detects and identifies selected bacterial, viral, and protozoan nucleic acids directly from EDTA whole blood collected from individuals with signs and/or symptoms of acute illness or recent acute febrile illness and known or suspected exposure to the following target pathogens: chikungunya virus (serotypes 1, 2, 3 and 4), Leptospira spp., and Plasmodium spp. (including 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.

Positive results do not rule out co-infections with pathogens not included on the BioFire Global Fever Panel. 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 and consultation of the CDC Yellow Book should be considered prior to use of the BioFire Global Fever Panel as some pathogens are more common in certain geographical locations.

For In Vitro Diagnostic Use.

The BioFire Global Fever Panel is a multiplexed nucleic acid-based test for the detection and identification of six pathogens which cause acute febrile illness (AFI) from whole blood specimens on BioFire FilmArray systems. The BioFire Global Fever Panel detects and identifies the following pathogens: chikungunya virus, dengue virus, Leptospira spp., and Plasmodium spp., including species differentiation between P. falciparum and P. vivax/ovale. The BioFire Global Fever Panel was originally described and was granted De Novo classification in DEN200043.

The BIOFIRE SHIELD Control Kit for the BioFire Global Fever Panel is an assayed quality control intended for monitoring the diagnostic performance of the BioFire Global Fever Panel. The Control Kit consists of Positive and Negative External Controls in a FilmArray Control Injection Vial format. The Positive External Control contains external assayed quality control material consisting of a set of non-infectious DNA segments dried on the filter of a FilmArray Control Injection Vial and detected by the Global Fever Panel. The Negative External Control contains no DNA and is also provided in the Control Injection Vial format. Analysis of the controls is carried out by specific pouch modules that are included in the BioFire Global Fever Panel Pouch Module Package. The BIOFIRE SHIELD Control Kit for the BioFire Global Fever Panel was fully described and cleared in K202382.

The purpose of this submission is to add BioFire FilmArray Torch as an additional instrument system for use with the BioFire Global Fever Panel and BIOFIRE SHIELD Control Kit for the BioFire Global Fever Panel, which were previously marketed for use with BioFire FilmArray 2.0 Systems. The FilmArray Torch is a modular configuration of the FilmArray 2.0 that minimizes instrument footprint by stacking up to twelve individual FilmArray Torch Modules on top of a single FilmArray Torch System Base. This 510(k) request describes modifications to the BioFire Global Fever Panel Pouch Module Package software and validation efforts to support adding FilmArray Torch Systems to the intended use of both the BioFire Global Fever Panel and associated BIOFIRE SHIELD Control Kit.

Here's an analysis of the provided text, focusing on the acceptance criteria and the study details:

1. Table of Acceptance Criteria and Reported Device Performance

The document doesn't explicitly state formal "acceptance criteria" in a separate section. Instead, the performance data is presented as a comparison to the predicate device (BioFire FilmArray 2.0 system), implying that non-inferiority or comparable performance to the established predicate is the implicit acceptance criterion.

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

• Test Set for BioFire Global Fever Panel (Table 3):

  • Sample Size: For each analyte (e.g., Leptospira interrogans), there were 3 concentrations tested (Moderate Positive, Low Positive, Negative). Each concentration was tested with 3 FilmArray 2.0 systems and 3 FilmArray Torch systems. On each system, 30 replicates were run.
    • For a single analyte and concentration, 30 replicates/system * 3 systems = 90 replicates for each platform.
    • Total replicates per analyte (3 concentrations): 90 replicates/platform * 3 concentrations = 270 replicates for each platform.
    • Total replicates across all analytes and concentrations for comparison: 1080 replicates on FilmArray 2.0 and 1080 replicates on FilmArray Torch.
    • The exact number of unique "samples" (batches of contrived material) is not specified, but the number of test runs is clear.
  • Data Provenance: The replicates are "contrived samples containing representative pathogens... at concentrations near the limit of detection (LoD)" and "negative samples containing no analyte." The exact country of origin is not stated, but the study was conducted by BioFire Defense, LLC (Salt Lake City, UT, USA). It is a prospective study as new testing was performed to evaluate the FilmArray Torch system.

• Test Set for BIOFIRE SHIELD Control Kit (Table 4):

  • Sample Size:
    • Positive External Controls: 135 replicates (45 replicates/system * 3 FilmArray Torch systems).
    • Negative External Controls: 135 replicates (45 replicates/system * 3 FilmArray Torch systems).
    • Total: 270 replicates.
  • Data Provenance: Details are for the BioFire FilmArray Torch platform only. The data is prospective, generated specifically for this evaluation.

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

For both studies (BioFire Global Fever Panel and BIOFIRE SHIELD Control Kit), the ground truth was established by the known concentration/presence of the analyte in the contrived samples or controls. While operators performed the tests, there is no mention of "experts" establishing the ground truth of the test material, as it's an analytical performance study using characterized samples.

4. Adjudication Method for the Test Set

There is no mention of an adjudication method in the context of expert review. The "expected result" for each test run (Detected/Not Detected) was based on the known composition of the contrived samples or control materials.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was Done, What was the Effect Size of How Much Human Readers Improve with AI vs. Without AI Assistance?

This type of study was not performed, nor is it applicable. The device is an in vitro diagnostic test that provides automated interpretation and report generation. There is no "human reader" component in the interpretation of the results to be improved by AI assistance. The document explicitly states: "Automated test interpretation and report generation; user cannot access raw data."

6. If a Standalone (i.e. Algorithm only without human-in-the-loop performance) was Done

Yes, a standalone study was done. The BioFire Global Fever Panel runs on the FilmArray system, which is an automated device. The performance data presented in Table 3 and Table 4 reflects the algorithm's performance (i.e., the device's ability to detect and identify targets) directly on the FilmArray Torch system, without human intervention in the result interpretation. The objective of this submission was to evaluate the performance of the existing panel on a new instrument system (FilmArray Torch), which itself is automated.

7. The Type of Ground Truth Used

The ground truth used was known composition of contrived samples/controls. This means:

• For positive samples, the specific analytes and their concentrations (e.g., 3xLoD, 1xLoD) were pre-determined.
• For negative samples and controls, the absence of the target analyte was pre-determined.

8. The Sample Size for the Training Set

The document does not provide information on a training set. This submission is for adding a new instrument system (BioFire FilmArray Torch) for an already existing and cleared device (BioFire Global Fever Panel). The "BioFire Global Fever Panel was originally described and was granted De Novo classification in DEN200043." Therefore, any initial development and potential "training" (if applicable for the underlying algorithm) would have occurred during the development phase for DEN200043, and those details are not part of this 510(k) summary. The current study is a verification/validation for expanded instrument compatibility.

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

As no training set information is provided in this document, the method for establishing its ground truth is also not available here.

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