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VITEK 2 AST-Gram Negative Cefazolin is designed for antimicrobial susceptibility testing of Gram-negative bacilli and is intended for use with the VITEK 2 Systems as a laboratory aid in the determination of in vitro susceptibility to antimicrobial agents.

VITEK 2 AST-Gram Negative Cefazolin (≤1-≥32 µg/mL) is a quantitative test. Testing is indicated for Enterobacterales (from infections other than uncomplicated UTI) as recognized by the FDA Susceptibility Test Interpretive Criteria (STIC).

VITEK 2 AST-Gram Negative Cefazolin (≤1-≥32 µg/mL) has demonstrated acceptable performance with the following organisms:

Enterobacterales (Escherichia coli, Proteus mirabilis, Klebsiella pneumoniae, Klebsiella oxytoca, Citrobacter koseri)

The VITEK 2 Gram Negative Susceptibility Card is intended for use with the VITEK 2 Systems in clinical laboratories as an in vitro test to determine the susceptibility of clinically significant aerobic Gram- negative bacilli to antimicrobial agents when used as instructed.

The principle of the VITEK® 2 AST cards is based on the microdilution minimum inhibitory concentration (MIC) technique reported by MacLowry and Marsh (1) and Gerlach (2). The VITEK® 2 AST card is essentially a miniaturized, abbreviated and automated version of the doubling dilution technique (3).

Each VITEK® 2 AST card contains 64 wells. A control well which only contains microbiological culture media is resident on all cards. The remaining wells contain premeasured portions of a specific antibiotic combined with culture media. The bacterial or yeast isolate to be tested is diluted to a standardized concentration with 0.45 – 0.5% saline before being used to rehydrate the antimicrobial medium within the card. The VITEK® 2 System automatically fills, seals and places the card into the incubator/reader. The VITEK® 2 Compact has a manual filling, sealing and loading operation. The VITEK® 2 Systems monitor the growth of each well in the card over a defined period of time. At the completion of the incubation cycle, a report is generated that contains the MIC value along with the interpretive category result for each antibiotic contained on the card.

VITEK® 2 AST-GN Cefazolin has the following concentrations in the card: 1, 2, and 8 (equivalent standard method concentration by efficacy in µg/mL).

The provided text describes the acceptance criteria and a study proving the device meets these criteria for the VITEK 2 AST-Gram Negative Cefazolin antimicrobial susceptibility testing system.

Here's a breakdown of the requested information:

1. Table of Acceptance Criteria and Reported Device Performance

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ETEST® is a manual, quantitative technique for the determination of antimicrobial susceptibility of non fastidious Gram negative and Gram positive aerobic bacteria and fastidious bacteria. The system comprises a predefined antibiotic gradient which is used to determine the Minimum Inhibitory Concentration (MIC, in μg/mL) of different antimicrobial agents against microorganisms tested on agar media after overnight incubation.

Testing with ETEST Imipenem/Relebactam P. aeruginosa (IRPA) (0.008/4-128/4 µg/mL) is indicated for Pseudomonas aeruginosa, as recognized by the FDA Susceptibility Test Interpretive Criteria (STIC).

The ETEST Imipenem/Relebactam P. aeruginosa (IRPA) (0.008/4-128/4 µg/mL) demonstrated acceptable performance with the following microorganism:
• Pseudomonas aeruginosa

ETEST® is a thin, inert and non-porous plastic strip carrying the MIC reading scale in μg/mL on one side and a predefined antibiotic gradient on the other side.

When the strip is applied to an inoculated agar surface, the preformed antibiotic gradient immediately transfers into the agar matrix, then forming a stable, continuous and exponential gradient of antibiotic concentrations directly underneath the strip. Bacterial growth becomes visible during incubation, and a symmetrical inhibition ellipse centered along the strip appears. The MIC value is read from the scale in terms of μg/mL at complete inhibition of bacterial growth, where the pointed end of the ellipse intersects the strip.

ETEST Imipenem/Relebactam P. aeruginosa (IRPA) with a concentration range of 0.008/4-128/4 µg/mL is specially designed and formulated for testing P. aeruginosa.

This document describes the regulatory clearance for the ETEST® Imipenem/Relebactam P. aeruginosa (IRPA) device, which is an antimicrobial susceptibility test. Here's a breakdown of the acceptance criteria and the study that proves the device meets them, based on the provided text:

Acceptance Criteria and Reported Device Performance

The acceptance criteria for this device are defined by established performance metrics in antimicrobial susceptibility testing, specifically Essential Agreement (EA) and Category Agreement (CA), compared to a reference method. The reported performance demonstrates the device meets these criteria.

Study Details Proving Device Meets Acceptance Criteria

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

   • Sample Size: 437 strains of Pseudomonas aeruginosa.
   • Data Provenance: The study involved external evaluations conducted with fresh and stock clinical isolates, as well as a set of challenge strains. The specific country of origin is not mentioned, but "external evaluations" imply samples from clinical settings. The nature of "fresh" and "stock clinical isolates" suggests a mix of retrospective and prospective data, where fresh isolates would be prospective and stock isolates could be retrospective.

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

   • This information is not explicitly provided in the document. Antimicrobial Susceptibility Testing (AST) generally relies on established laboratory methods rather than expert consensus for ground truth, but the personnel performing the reference method would be trained laboratory technicians.

3. Adjudication Method for the Test Set:

   • None explicitly stated as it's a comparison to a reference laboratory method (CLSI M07-11th Ed broth microdilution). Discrepancy resolution (adjudication) is typically less relevant for quantitative laboratory assays where results are directly compared to a gold standard.

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

   • No, a MRMC study was not done. This is an automated/manual laboratory test for determining Minimum Inhibitory Concentration (MIC), not an imaging device requiring human reader interpretation in a diagnostic workflow. The "human-in-the-loop" aspect for this device is the application of the strip and reading the MIC, which is part of the validation for the device's accuracy against a gold standard method.

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

   • This concept does not directly apply to this type of device. The ETEST device itself is a "standalone" test. The performance reported (EA and CA) is the performance of the ETEST system (strip + reading methodology) compared to the reference broth microdilution method. It inherently involves a human reading the result by interpreting the inhibition ellipse on the strip. The note "b) In the ETEST® Imipenem/Relebactam clinical studies, swabs were used for plate inoculation/streaking and forceps were used for ETEST® strip application. Testing with the optional Inoculator RETRO C80™, Vacuum Pen NEMA C88™ and Applicator SIMPLEX C76™ was not evaluated during the clinical studies" suggests that human manual steps were involved in the performance evaluation.

6. The Type of Ground Truth Used:

   • Reference Method: The ground truth was established by the CLSI M07-11th Ed (January 2018) broth microdilution reference method, following specifications as defined in CLSI M100 34th Ed. (February 2024). This is considered the gold standard for antimicrobial susceptibility testing. Outcomes data or pathology are not relevant for this type of in vitro diagnostic device.

7. The Sample Size for the Training Set:

   • The document does not mention a training set in the context of machine learning or AI models. This device is a manual, quantitative laboratory test (an ETEST strip system) and not an AI/ML-driven diagnostic. Therefore, there's no "training set" in the typical sense of AI development. The "strains" mentioned are for the performance evaluation against the reference method.

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

   • As there is no mention of a training set for an AI/ML model, this question is not applicable. The device's performance is validated against a well-established reference laboratory method using a test set of clinical isolates and challenge strains.

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The VITEK® COMPACT PRO is intended for the automated quantitative and/or qualitative antimicrobial susceptibility testing of isolated colonies for most clinically significant aerobic Gram-negative bacilli, Staphylococcus spp., Enterococcus spp., Streptococcus spp., and yeast.

The VITEK® COMPACT PRO is also intended for the automated identification of most clinically significant anaerobic organisms and Corynebacterium species, fermenting and nonfermenting Gram-negative bacilli, Gram-positive organisms, fastidious organisms, and yeasts and yeast-like organisms.

The VITEK® COMPACT PRO instrument is an automated instrument designed for use in low-to medium-range applications in both Clinical and Industry laboratories. The instrument performs sample well filling, incubation, and optical readings. The VITEK® COMPACT PRO instrument is a two-step automated instrument for:

• Hydrating reagents with sample inoculum
• Pre-processing cards, incubating cards, and continuous reading for growth

The VITEK® 2 Systems Software receives the instrument optical readings and performs analysis. The instrument then ejects the completed reagent card into the waste area for disposal.

The system includes a VITEK® COMPACT PRO instrument with an internal computer, monitor, keyboard, mouse, handheld barcode scanner, and USB hub. The software provided with the internal computer includes analysis and limited data management programs. A bidirectional computer interface (BCI) may transfer results automatically to the user's laboratory information system (LIS).

A Quality Control System is available to track the quality control results of the test cards. The Advanced Expert System™ (Clinical Use) is available to provide online, systematic validation of results and interpretation of resistant phenotypes found during susceptibility testing.

The provided text describes the regulatory clearance of a medical device, the VITEK® COMPACT PRO, and its performance evaluation. However, it does not explicitly define "acceptance criteria" in a table format with specific numerical targets. Instead, it details the results of various performance tests as evidence that the device meets acceptable standards, primarily by demonstrating substantial equivalence to a predicate device.

Here's an interpretation of the acceptance criteria and study that can be extracted from the provided information:

Interpretation of Acceptance Criteria and Study Design:

The VITEK® COMPACT PRO is an automated antimicrobial susceptibility testing system. The core of its acceptance criteria and the study proving it meets these criteria relies on demonstrating substantial equivalence to a previously cleared VITEK® 2 System (N50510 Supplement S082). This means the new device must perform comparably to the predicate device across various metrics.

1. Table of Acceptance Criteria (Inferred) and Reported Device Performance:

Since explicit acceptance criteria are not tabulated with thresholds, they are inferred from the reported performance, with the implicit criterion being "comparable to or better than the predicate device."

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

• QC Testing: Each of the 13 quality control organisms was tested at least twenty times. This testing was conducted at "at least three of the clinical evaluation trial sites."
• Reproducibility: Isolates were tested in triplicate for three trial sites. Individual test sets were selected for each antimicrobial, with each set including a minimum of 10 strains (at least 2 with on-scale results).
• Clinical Performance Evaluation: "Representative, clinically relevant strains" were tested. Each strain was tested one time with both the VITEK® COMPACT PRO and the VITEK® 2.
• Data Provenance: The document states testing was done at "at least three of the clinical evaluation trial sites" for QC and "three trial sites" for reproducibility. The country of origin for these sites is not specified, but bioMérieux Inc. is located in Hazelwood, Missouri, USA, implying the studies were likely conducted in the US. The studies appear to be prospective as they involve new testing of isolates for performance evaluation.

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

This information is not explicitly stated in the provided text. The ground truth for the clinical performance evaluation was established by comparing the VITEK® COMPACT PRO's results against the VITEK® 2 System's results (N50510 Supplement S082), which implicitly serves as the "expert consensus" or "reference method" in this context. The document does not describe a separate human expert panel for adjudication or ground truth establishment the way it might for an AI imaging device.

4. Adjudication Method for the Test Set:

Not applicable in the traditional sense of human expert adjudication. The comparison was directly between the new device (VITEK® COMPACT PRO) and the predicate device (VITEK® 2 System) for MICs and interpretations (S/SDD/I/R). There's no mention of a 2+1 or 3+1 human expert adjudication process.

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, an MRMC study was not done. This device is an automated in vitro diagnostic instrument, not an AI-assisted imaging device for human interpretation. The comparison is machine-to-machine (new instrument vs. predicate instrument).

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

Yes, the primary performance evaluation was a standalone "algorithm only" (instrument only) performance comparison. The VITEK® COMPACT PRO (device under test) generated MICs and interpretations, and these were directly compared to those generated by the predicate VITEK® 2 System. Human "in-the-loop" performance is not relevant for the core function of this automated susceptibility system in the context of its performance study.

7. The type of ground truth used:

The ground truth for the clinical performance evaluation was the MIC results and categorical interpretations (S/SDD/I/R) obtained from the legally marketed predicate device, the VITEK® 2 System (N50510 Supplement S082). This serves as the reference method against which the new device's performance is measured.

8. The Sample Size for the Training Set:

The document does not discuss a separate "training set" in the context of device development or performance evaluation. This is not an AI/ML device where a distinct training dataset is typically used. The development process likely involved internal verification and validation, but the reported studies (QC, Reproducibility, Clinical Performance) are essentially testing/validation datasets.

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

Not applicable, as no explicit training set for an AI/ML algorithm is described.

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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.

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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).

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VITEK 2 AST-Yeast Voriconazole is designed for antifungal susceptibility testing of Candida species and is intended for use with the VITEK 2 and VITEK 2 Compact Systems as a laboratory aid in the determination of in vitro susceptibility to antifungal agents. VITEK 2 AST-Yeast Voriconazole is a quantitative test. Voriconazole has been shown to be active against most strains of the microorganisms listed below, according to the FDA label for this antifungal.

Active in vitro and in clinical infections: Candida krusei Candida parapsilosis Candida tropicalis

The VITEK 2 Fungal Susceptibility Card is intended for use with the VITEK 2 Systems in clinical laboratories as an in vitro test to determine the susceptibility of clinically significant yeasts to antifungal agents when used as instructed.

The principle of the VITEK® 2 AST cards is based on the microdilution minimum inhibitory concentration (MIC) technique. The VITEK® 2 AST card is essentially a miniaturized, abbreviated and automated version of the doubling dilution technique. Each VITEK® 2 AST card contains 64 wells. A control well which only contains microbiological culture media is resident on all cards. The remaining wells contain premeasured portions of a specific antibiotic combined with culture media. The bacterial or yeast isolate to be tested is diluted to a standardized concentration with 0.45-0.5% saline before being used to rehydrate the antimicrobial medium within the card. The VITEK® 2 System automatically fills, seals and places the card into the incubator/reader. The VITEK® 2 Compact has a manual filling, sealing and loading operation. The VITEK® 2 Systems monitor the growth of each well in the card over a defined period of time. At the completion of the incubation cycle, a report is generated that contains the MIC value along with the interpretive category result for each antibiotic contained on the card.

VITEK® 2 AST-YS Voriconazole has the following concentrations in the card: 0.03125, 0.125, 0.25, 1, and 2 (equivalent standard method concentration by efficacy in ug/mL).

The provided FDA 510(k) summary describes the VITEK® 2 AST-Yeast Voriconazole device, which is an antimicrobial susceptibility test system.

Here's an analysis of the acceptance criteria and the study that proves the device meets them:

1. Table of Acceptance Criteria and Reported Device Performance:

The acceptance criteria are implicitly derived from the FDA Class II Special Controls Guidance Document: Antimicrobial Susceptibility Test (AST) Systems and are presented through "Essential Agreement" (EA) and "Category Agreement" (CA) performance metrics, along with error rates. The table below summarizes the reported performance for each microorganism. The specific acceptance thresholds for EA and CA are not explicitly stated as numerical percentages (e.g., >90% EA, >90% CA) with the exception of the individual error types (VME, ME, mE) having specified maximum allowable percentages. However, it is implied that the presented results were deemed acceptable by the FDA.

Key Definitions:

• Essential Agreement (EA): Agreement between the MIC results of the test device and the reference method within plus or minus one doubling dilution.
• Category Agreement (CA): Agreement between the interpretive categories (Susceptible, Intermediate, Resistant) of the test device and the reference method.
• Very Major Error (VME): The test device reports susceptible, but the reference method reports resistant.
• Major Error (ME): The test device reports resistant, but the reference method reports susceptible.
• Minor Error (mE): Any other disagreement in interpretive category (e.g., susceptible vs. intermediate, resistant vs. intermediate).

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

The sample sizes for the test set (external evaluation) are provided for each microorganism:

• C. albicans: 257 isolates
• C. krusei: 76 isolates
• C. parapsilosis: 74 isolates
• C. tropicalis: 87 isolates

Data Provenance: The study conducted an "external evaluation" with "fresh and stock clinical isolates, as well as a set of challenge strains." The document does not specify the country of origin of the data nor explicitly state if it was retrospective or prospective. However, "fresh clinical isolates" typically implies a prospective collection, while "stock clinical isolates" could be either.

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

The ground truth was established by the "CLSI broth microdilution reference method." This is a standardized laboratory method, not reliant on human expert adjudication in the same way an imaging study would be. Therefore, the concept of "experts" and their qualifications as typically applied to visual diagnostic tasks (e.g., radiologists) is not directly applicable here. The ground truth method itself (CLSI broth microdilution) is the expert-defined standard.

4. Adjudication Method for the Test Set:

Not applicable in the human expert sense. The "adjudication method" for determining the ground truth in this context is the CLSI broth microdilution reference method, which serves as the gold standard for antimicrobial susceptibility testing. The device's results are compared directly against this established reference.

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 where human readers interpret results, often in conjunction with AI. The VITEK® 2 AST-Yeast Voriconazole is an automated in vitro diagnostic device for antimicrobial susceptibility testing; its performance is evaluated by comparing its automated output to a gold standard laboratory method, not by how it assists human readers.

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

Yes, a standalone performance evaluation was done. The VITEK® 2 AST-Yeast Voriconazole system is an automated device designed to determine antimicrobial susceptibility without human interpretation of the primary data once the sample is loaded. The performance metrics (Essential Agreement, Category Agreement, error rates) directly reflect the device's standalone capability compared to the reference method.

7. The Type of Ground Truth Used:

The ground truth used was the CLSI broth microdilution reference method, incubated for 24 hours (up to 48 hours for slowly growing isolates). This is a well-established and scientifically accepted standard in microbiology for determining minimum inhibitory concentrations (MICs) of antifungal agents.

8. The Sample Size for the Training Set:

The document does not explicitly state the sample size for the training set. The descriptions focus on the "external evaluation" (test set). For IVD devices like this, the 'training set' often corresponds to historical data, internal studies, and method development efforts that lead to the final algorithm and concentration ranges. Without further information, the exact size of the training set used to develop the VITEK® 2 AST-Yeast Voriconazole algorithm is not provided in this 510(k) summary.

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

Similar to the answer for point 8, the document does not explicitly describe how the ground truth for any potential training set was established. However, given that the final performance is benchmarked against the CLSI broth microdilution reference method, it is highly probable that any internal development or training data would also have used this or a similar established reference method to determine the true susceptibility of isolates.

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VITEK 2 AST-Yeast Anidulafungin is designed for antifungal susceptibility testing of Candida species and is intended for use with the VITEK 2 and VITEK 2 Compact Systems as a laboratory aid in the determination of in vitro susceptibility to antifungal agents. VITEK 2 AST-Yeast Anidulafungin is a quantitative test. Anidulafungin has been shown to be active against most strains of the microorganisms listed below, according to the FDA label for this antifungal.

Active in vitro and in clinical infections: Candida albicans Candida glabrata Candida parapsilosis Candida tropicalis

In vitro data are available, but clinical significance is unknown: Candida guillermondii Candida krusei

The VITEK 2 Fungal Susceptibility Card is intended for use with the VITEK 2 Systems in clinical laboratories as an in vitro test to determine the susceptibility of clinically significant yeasts to antifungal agents when used as instructed.

The principle of the VITEK® 2 AST cards is based on the microdilution minimum inhibitory concentration (MIC) technique reported by MacLowry and Marsh (1) and Gerlach(2). The VITEK® 2 AST card is essentially a miniaturized, abbreviated and automated version of the doubling dilution technique (3).

Each VITEK® 2 AST card contains 64 wells. A control well which only contains microbiological culture media is resident on all cards. The remaining wells contain premeasured portions of a specific antibiotic combined with culture media. The bacterial or yeast isolate to be tested is diluted to a standardized concentration with 0.45 – 0.5% saline before being used to rehydrate the antimicrobial medium within the card. The VITEK® 2 System automatically fills, seals and places the card into the incubator/reader. The VITEK® 2 Compact has a manual filling, sealing and loading operation. The VITEK® 2 Systems monitor the growth of each well in the card over a defined period of time. At the completion of the incubation cycle, a report is generated that contains the MIC value along with the interpretive category result for each antibiotic contained on the card.

VITEK® 2 AST-YS Anidulafungin has the following concentrations in the card: 0.0625, 0.125, 0.5, 2, and 8 (equivalent standard method concentration by efficacy in ug/mL).

Here's an analysis of the acceptance criteria and the study proving the device meets those criteria, based on the provided text.

Device: VITEK 2 AST-Yeast Anidulafungin

Indications for Use: Antifungal susceptibility testing of Candida species (C. albicans, C. glabrata, C. parapsilosis, C. tropicalis, C. guilliermondii, C. krusei) as a laboratory aid in determining in vitro susceptibility to antifungal agents.

1. Table of Acceptance Criteria and Reported Device Performance

The provided document doesn't explicitly state the acceptance criteria in a separate table directly defining thresholds for Essential Agreement (EA), Category Agreement (CA), or error rates (VME, ME, mE) that the device must meet for approval. Instead, it presents the results of the performance study and implies that these results were deemed "acceptable" by the FDA. The performance is compared to the "CLSI broth microdilution reference method, as defined in the FDA Class II Special Controls Guidance Document: Antimicrobial Susceptibility Test (AST) Systems; Guidance for Industry and FDA (Issued August 28, 2009)". This guidance document would contain the specific acceptance criteria.

However, based on the presented "Performance Overview" (Page 7) and the overall context of AST device approvals, typical acceptance criteria for Essential Agreement and Category Agreement are usually in the range of 90-95% or higher, with Very Major Error (VME) and Major Error (ME) rates usually being low (e.g.,

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The VIDAS® TBI (GFAP, UCH-L1) test is composed of two automated assays - VIDAS® TBI (GFAP) and VIDAS® TBI (UCH-L1) - to be used on the VIDAS® 3 instrument for the quantitative measurement of Glial Fibrillary Acidic Protein (GFAP) and Ubiquitin C-terminal Hydrolase (UCH-L1) in human serum using the ELFA (Enzyme Linked Fluorescent Assay) technique. The results of both assays are requred to obtain an overall qualitative test interpretation.

The overall qualitative VIDAS® TBI (GFAP, UCH-L1) test result is used, in conjunction with clinical information, to aid in the evaluation of patients (18 years of age or older), presenting within 12 hours of suspected mild traumatic brain injury (Glasgow Coma Scale score 13-15), to assist in determining the need for a Computed Tomography (CT) scan of the head. A negative interpretation of VIDAS® TBI (GFAP, UCH-L1) test is associated with the absence of acute intracranial lesions visualized on a head CT scan.

The VIDAS® TBI (GFAP, UCH-L1) test is composed of two automated assays – VIDAS® TBI (GFAP) and VIDAS® TBI (UCH-L1) – to be used on the VIDAS® 3 instrument. Similar to other VIDAS assays, VIDAS TBI (GFAP) and VIDAS TBI (UCH-L1) test kits (specific to each biomarker) contain the solid phase receptacles (SPRs®), the reagent strips, Product Calibrator S1 and Product Control C1. These test kits will also contain the master lot entry (MLE) data i.e., a barcode printed on the outer label of the packaging, as well as the reference number of the package insert to download from the bioMérieux website.

Whether it be for the GFAP or UCH-L1 quantification, the test combines a three-step enzyme immunoassay sandwich method with a final fluorescent detection step, also known as enzyme-linked fluorescent assay (ELFA).

The Solid Phase Receptacle (SPR) serves as the solid phase as well as the pipetting device. The inner surface of the SPR is coated with antibodies aqainst the substance of interest i.e., anti-GFAP or anti-UCH-L1 antibodies. The reagent strip consists of 10 wells covered with a labeled foil seal. Well 1 is designated for the sample. Eight of the wells contain sample diluent, wash buffer, conjugate, and tracer. The last well contains the fluorescent substrate. All of the assay steps are performed automatically by the instrument.

The intensity of the fluorescence is proportional to the concentration of the analyte the sample. At the end of the assay, the biomarker concentration is automatically calculated by the instrument in relation to the calibration curve and stored in the Master Lot Entry (MLE) data.

VIDAS TBI (GFAP) and VIDAS TBI (UCH-L1) results are reported separately: the VIDAS 3 reports the calculated concentration and the qualitative interpretation for each. The final result i.e., the patient's status in relation to suspected mild traumatic brain injury, must be interpreted by the user according to the decision tree presented in the package insert.

This document describes the validation of the VIDAS® TBI (GFAP, UCH-L1) test, an automated assay for diagnosing mild traumatic brain injury. The submission compares the device to a predicate device, the BANYAN BTI™, and summarizes non-clinical and clinical testing results. The following points address the requested information based on the provided text:

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

The document does not explicitly state "acceptance criteria" for each performance metric in a table format. However, it presents the results of various assays and often implies that the results "demonstrate" or "confirm" the required performance, indicating these are the achieved results compared to an internal standard or regulatory expectation. Below is a table summarizing various performance metrics and their reported results. Specific acceptance criteria values are not provided in this public summary.

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

• Test set sample size: For the diagnostic accuracy study, the sample size is not explicitly stated but refers to the "ALERT cohort." For the reference interval study, 513 apparently healthy US adult subjects were used.
• Data provenance: The diagnostic accuracy study was performed using the "ALERT cohort." The reference interval study was conducted at three sites (one internal European site and two external US sites). It is not specified whether these studies were retrospective or prospective, though "ALERT cohort" could suggest a pre-existing dataset.

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. The diagnostic accuracy study compares the device's results to the presence/absence of acute intracranial lesions visualized on a head CT scan, but the number or qualifications of experts interpreting these CT scans to establish ground truth are not mentioned.

4. Adjudication method (e.g., 2+1, 3+1, none) 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, If so, what was the effect size of how much human readers improve with AI vs without AI assistance

A multi-reader multi-case (MRMC) comparative effectiveness study was not performed. This device is an in vitro diagnostic test for quantitative measurement of biomarkers, not an AI-assisted imaging device that impacts human reader performance.

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

Yes, the diagnostic accuracy study presents the standalone performance of the VIDAS® TBI (GFAP, UCH-L1) assay. The results (sensitivity, specificity, etc.) are based on the device's output compared to the ground truth (CT scan findings). The device is used "in conjunction with clinical information," but the reported diagnostic accuracy figures are for the test itself.

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

The ground truth for the diagnostic accuracy study was "absence of acute intracranial lesions visualized on a head CT scan." This indicates that CT scan results were used as the reference standard for traumatic brain injury assessment.

8. The sample size for the training set

This document describes a diagnostic device and its validation. It does not explicitly mention a "training set" in the context of machine learning or AI models with distinct training and test phases. The "test set" for diagnostic accuracy is referred to as the "ALERT cohort." The reference interval was established using 513 apparently healthy subjects.

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

As there is no explicitly defined "training set" for an AI model in this submission, the method for establishing ground truth for a training set is not applicable or described. The clinical performance data presented (Diagnostic Accuracy and Reference interval) seems to represent the evaluation of the final device.

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VITEK® 2 AST-Gram Positive Lefamulin is designed for antimicrobial susceptibility testing of Gram positive microorganisms and is intended for use with the VITEK® 2 and VITEK® 2 Compact Systems as a laboratory aid in the determination of in vitro susceptibility to antimicrobial agents.

VITEK® 2 AST-Gram Positive Lefamulin is a quantitative test. Lefamulin has been shown to be active against most strains of the microorganisms listed below, according to the FDA label for this antimicrobial.

Active both in vitro and in clinical infections: Staphylococcus aureus (methicillin-susceptible isolates)

The VITEK® 2 Gram-positive Susceptibility Card is intended for use with the VITEK® 2 Systems in clinical laboratories as an in vitro test to determine the susceptibility of Staphylococcus spp., and S. agalactive to antimicrobial agents when used as instructed.

The principle of the VITEK® 2 AST cards is based on the microdilution minimum inhibitory concentration (MIC) technique reported by MacLowry and Marsh (1) and Gerlach (2). The VITEK® 2 AST card is essentially a miniaturized, abbreviated and automated version of the doubling dilution technique (0).

Each VITEK® 2 AST card contains 64 wells. A control well which only contains microbiological culture media is resident on all cards. The remaining wells contain premeasured portions of a specific antibiotic combined with culture media. The bacterial or yeast isolate to be tested is diluted to a standardized concentration with 0.45 - 0.5% saline before being used to rehydrate the antimicrobial medium within the card. The VITEK® 2 System automatically fills, seals and places the card into the incubator/reader. The VITEK® 2 Compact has a manual filling, sealing and loading operation. The VITEK® 2 Systems monitor the growth of each well in the card over a defined period of time. At the completion of the incubation cycle, a report is generated that contains the MIC value along with the interpretive category result for each antibiotic contained on the card.

VITEK® 2 AST-GP Lefamulin (≤ 0.03 –>4 µg/mL) has the following concentrations in the card: 0.125, 0.5, 1, and 2 (equivalent standard method concentration by efficacy in ug/mL).

The VITEK® 2 AST-Gram Positive Lefamulin (≤ 0.03 - ≥4 µg/mL) device is an antimicrobial susceptibility testing system designed for Gram-positive microorganisms. The acceptance criteria and performance of the device are detailed below.

1. Table of Acceptance Criteria and Reported Device Performance

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

The test set included:

• 404 isolates for Essential Agreement reporting and 404 isolates for Category Agreement reporting (derived from the numerators/denominators in Table 2).
• 3 resistant isolates were tested for VME (Very Major Error)
• 401 susceptible isolates were tested for ME (Major Error)

The data provenance is described as an "external evaluation" conducted with "fresh and stock clinical isolates, as well as a set of challenge strains." The document does not specify the country of origin of the data or explicitly state whether the study was retrospective or prospective.

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 text.

4. Adjudication method for the test set

This information is not provided in the given text.

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

A multi-reader multi-case (MRMC) comparative effectiveness study with human readers assisted by AI is not applicable to this device. This device is an automated antimicrobial susceptibility test system, not an AI-assisted diagnostic tool interpreted by human readers.

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

Yes, a standalone performance evaluation was done. The VITEK® 2 AST-GP Lefamulin system's performance was compared directly to the CLSI broth microdilution reference method (the ground truth), without human intervention in the interpretation of the VITEK® 2 results. The system automatically generates MIC values and interpretive categories.

7. The type of ground truth used

The ground truth used was the CLSI broth microdilution reference method, incubated at 16-20 hours.

8. The sample size for the training set

The document does not explicitly mention a separate "training set" or its sample size. The description focuses on the external evaluation data used for performance assessment. As an AST system, the device's "training" for MIC determination is inherent in its design based on established microdilution principles and may not involve a distinct, large-scale machine learning training set in the way an AI algorithm might.

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

Since a distinct training set is not explicitly mentioned as per the prompt's context (e.g., for an AI algorithm), details on how its ground truth was established are not provided. The device's operation is based on established microbiological principles, and its performance is validated against the CLSI broth microdilution reference method.

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VITEK® 2 Streptococcus Penicillin is designed for antimicrobial susceptibility testing of Streptococcus species and is intended for use with the VITEK® 2 and VITEK® 2 Compact Systems as a laboratory aid in the determination of in vitro susceptibility to antimicrobial agents. VITEK® 2 Streptococcus Penicillin is a quantitative test. Penicillin has been shown to be active against most strains of the microorganisms listed below, according to the FDA label for this antimicrobial.

Active both in vitro and in clinical infections: Beta hemolytic Streptococci groups C and G Streptococcus pyogenes Streptococcus agalactiae Streptococcus viridans group Streptococcus pneumoniae

The VITEK® 2 Streptococcus Susceptibility Card is intended for use with the VITEK® 2 Systems in clinical laboratories as an in vitro test to determine the susceptibility of Sireptococcus pneumoniae, beta-hemolytic Streptococcus, and Viridans Streptococcus to antimicrobial agents when used as instructed.

The principle of the VITEK® 2 AST cards is based on the microdilution minimum inhibitory concentration (MIC) technique reported by MacLowry and Marsh(1) and Gerlach(2). The VITEK® 2 AST card is essentially a miniaturized, abbreviated and automated version of the doubling dilution technique(3).

Each VITEK® 2 AST card contains 64 wells. A control well which only contains microbiological culture media is resident on all cards. The remaining wells contain premeasured portions of a specific antibiotic combined with culture media. The bacterial or yeast isolate to be tested is diluted to a standardized concentration with 0.45 - 0.5% saline before being used to rehydrate the antimicrobial medium within the card. The VITEK® 2 System automatically fills, seals and places the card into the incubator/reader. The VITEK® 2 Compact has a manual filling, sealing and loading operation. The VITEK® 2 Systems monitor the growth of each well in the card over a defined period of time. At the completion of the incubation cycle, a report is generated that contains the MIC value along with the interpretive category result for each antibiotic contained on the card.

VITEK® 2 Streptococcus Penicillin has the following concentrations in the card: 0.06, 0.12, 0.5, and 2ug/mL (equivalent standard method concentration by efficacy in ug/mL).

Here's a summary of the acceptance criteria and study details for the VITEK® 2 Streptococcus Penicillin device:

1. Acceptance Criteria and Reported Device Performance

The device performance is compared to the broth microdilution reference method. The key metrics are Essential Agreement (EA) and Category Agreement (CA), along with Very Major Errors (VME), Major Errors (ME), and Minor Errors (mE).

The document states that the device "demonstrated substantially equivalent performance when compared with the broth microdilution reference method, as defined in the FDA Class II Special Controls Guidance Document: Antimicrobial Susceptibility Test (AST) Systems; Guidance for Industry and FDA (Issued August 28, 2009)." This guidance document typically outlines specific numerical acceptance criteria for EA, CA, VME, ME, and mE, which are implicitly met by the reported percentages being considered "acceptable."

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

The sample sizes for the test set are embedded within the "Reported Device Performance" column (e.g., 350 for Streptococcus pneumoniae (non-meningitis), 391 for Streptococcus Viridans group, 833 for Beta-hemolytic Streptococcus).

The data provenance is from "external evaluation... conducted with fresh and stock clinical isolates, as well as a set of challenge strains." This implies a combination of retrospective (stock clinical isolates) and prospective (fresh clinical isolates) data. The country of origin of the data is not specified in the provided text.

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

This information is not provided in the document. The ground truth is established by the CLSI broth microdilution reference method, but details on expert involvement in this process (e.g., reading/interpreting the reference method results) are not mentioned.

4. Adjudication Method for the Test Set

This information is not explicitly provided in the document. The study compares the VITEK® 2 results to the CLSI broth microdilution reference method. Adjudication might be part of the standard CLSI method, but it is not detailed here for discrepancies.

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

No, a multi-reader multi-case (MRMC) comparative effectiveness study was not done. This study focuses on the performance of an automated diagnostic device against a reference method, not on human reader performance with or without AI assistance.

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

Yes, a standalone performance study was done. The VITEK® 2 system is a "Fully Automated Short-Term Incubation Cycle Antimicrobial Susceptibility System," and its performance was evaluated against the CLSI broth microdilution reference method. This is an evaluation of the algorithm's output (MIC values and interpretive categories) without direct human intervention in the interpretation of the VITEK® 2 results.

7. The Type of Ground Truth Used

The type of ground truth used is the broth microdilution reference method, specifically the CLSI method incubated at 16-20 hours. This is typically considered the gold standard for antimicrobial susceptibility testing.

8. The Sample Size for the Training Set

The document does not explicitly state the sample size for the training set. The study describes "external evaluation" for performance, but it doesn't separate out a specific training set size for the VITEK® 2 algorithm itself.

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

The document does not explicitly state how the ground truth for any training set was established, as it primarily focuses on the performance evaluation of the final device against a reference method. However, given that the device is an "Automated quantitative antimicrobial susceptibility test," it's highly probable that any internal training/development would have used an established reference method (like broth microdilution) to establish ground truth for algorithm development.

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