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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.

Ask a specific question about this device

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® 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. This includes: clinical signs and symptoms associated 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 influenza
• · 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
• · КРС
• · 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 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 cariers 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 FilmArray Pneumonia Panel plus is designed to simultaneously identify MERS-CoV and 26 potential pathogens of lower respiratory tract infection (LRTI) and associated antimicrobial resistance (AMR) genes from a sputum-like (induced and expectorated sputum as well as endotracheal aspirate, ETA) or bronchoalveolar lavage (BAL)-like (BAL and mini-BAL) specimens obtained from individuals meeting MERS-CoV clinical and/or epidemiological criteria in a time (~1 hour). The FilmArray Pneumonia Panel plus is compatible with BioFire Diagnostics' (BioFire) PCR-based in vitro diagnostic BioFire FilmArray 2.0 (K143178) and BioFire FilmArray Torch (K160068) systems for infectious disease testing. A specific software module (i.e., FilmArray Pneumonia Panel plus pouch module) is used to perform FilmArray Pneumonia Panel plus testing on these systems.

A test is initiated by loading Hydration Solution into one port of the FilmArrav pouch and a soutumlike or BAL-like sample mixed with the provided Sample Buffer into the port of the FilmArray Pneumonia Panel plus pouch and placing it in a FilmArray instrument. The pouch contains all the reagents required for specimen testing and analysis in a freeze-dried format; the addition of Hydration Solution and Sample/Buffer Mix rehydrates the reagents. After the pouch is prepared, the FilmArray Software quides the user though the steps of placing the pouch into the instrument, scanning the pouch barcode, entering the sample identification, and initiating the run.

The FilmArray instrument contains a coordinated system of inflatable bladders and seal points, which act on the pouch to control the movement of liquid between the pouch blisters. When a bladder is inflated over a reagent blister, it forces liquid from the blister into connecting channels. Alternatively, when a seal is placed over a connecting channel it acts as a valve to open or close a channel. In addition, electronically-controlled pneumatic pistons are positioned over multiple plungers in order to deliver the rehydrated reagents into the blisters at the appropriate times. Two Peltier devices control heating and cooling of the pouch to drive the PCR reactions and the melt curve analysis.

Nucleic acid extraction occurs within the FilmArray pouch using mechanical and chemical lvsis followed by purification using standard magnetic bead technology. After extracting and purifying nucleic acids from the unprocessed sample, the FilmArray performs a nested multiplex PCR that is executed in two stages. During the first stage, the FilmArray performs a single, large volume, highly multiplexed reverse transcription PCR (rt-PCR) reaction. The products from first stage PCR are then diluted and combined with a fresh, primer-free master mix and a fluorescent double stranded DNA binding dye (LC Green Plus, BioFire Diagnostics). The solution is then distributed to each well of the array. Array wells contain sets of primers designed specifically to amplify sequences internal to the PCR products generated during the first stage PCR reaction. The 2nd stage PCR, or nested PCR, is performed in singleplex fashion in each well of the array. At the 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 FilmArray Software automatically interprets the results of each DNA melt curve analysis and combines the data with the results of the internal pouch controls to provide a test result for each organism on the panel.

The provided text is a summary of a Special 510(k) submission for the BioFire FilmArray Pneumonia Panel plus. The purpose of this submission is solely to modify the labeling of the device to include new limitations regarding the Adenovirus2 assay's performance closer to its expiration date.

Therefore, the document does not describe a new study to prove device performance against acceptance criteria. Instead, it refers to a problem identified through stability studies and a voluntary recall. The premise of this 510(k) submission is that because there are no changes to the actual device, its fundamental scientific technology, performance, and risk are unchanged from the legally marketed predicate device (K181324).

The acceptance criteria table below is inferred from the identified issue and the proposed label modifications, not from a performance study demonstrating device capabilities.

Acceptance Criteria and Reported Device Performance

Study Details (Based on the information provided)

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

   • The document does not explicitly state the sample size of the test set used in the stability study that identified the Adenovirus C issue.
   • The data provenance is from stability studies conducted by BioFire Diagnostics, LLC. It is retrospective in the sense that the issue was discovered after initial marketing and through ongoing stability monitoring of manufactured product.

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

   • This information is not provided as the document describes a stability study related to device shelf-life rather than a diagnostic performance study against a clinical ground truth. The "ground truth" here would have been the presence/absence and concentration of adenovirus species C in the stability samples, likely confirmed by a reference method in a laboratory setting. Details on experts or their qualifications are not given.

3. Adjudication method for the test set:

   • This information is not provided. Given it's a stability study on a diagnostic assay, adjudication in the context of expert consensus on clinical cases is not directly applicable. The determination of "false negative" would have been based on comparison to expected results or a reference method.

4. 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 comparative effectiveness study was not done. This device is a multiplexed nucleic acid test (an in vitro diagnostic device), not an imaging AI device that involves human readers.

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

   • The FilmArray Pneumonia Panel plus is an automated diagnostic assay. Its performance (detection of nucleic acids) is inherently "standalone" in the sense that the instrument and software interpret the results without human interpretation of raw data. The stability study assessed this standalone performance.

6. The type of ground truth used:

   • For the stability studies that identified the issue, the ground truth was likely analytical truth (known presence, absence, and concentration of specific analytes like Adenovirus species C) in manufactured control samples or spiked specimens. This is standard for stability testing of IVD assays.

7. The sample size for the training set:

   • This document describes a modification to labeling based on post-market stability findings, not a de novo development or training of an algorithm. Therefore, information about a "training set" is not applicable and not provided.

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

   • As there is no mention of a training set for an algorithm, this information is not applicable.

Ask a specific question about this device

The FilmArray® Pneumonia Panel is a multiplexed nucleic acid test intended for use with FilmArray® 2.0 or FilmArray® Torch systems for the simultaneous detection of 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 suspected of lower respiratory tract infection.

The following bacteria are reported semi-quantitatively with bins representing approximately 10^4, 10^5 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 -Adenovirus

• -Coronavirus

• -Human Metapneumovirus

• -Human Rhinovirus/Enterovirus

• -Influenza A

• -Influenza B

• -Parainfluenza Virus

• -Respiratory Syncytial Virus

Antimicrobial Resistance Genes -CTX-M -IMP -KPC -NDM -OXA-48-like -VIM -mecA/C and MREJ

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 FilmArray 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 FilmArray Pneumonia Panel are not equivalent to CFU/mL and do not consistently correlate with the quantity of bacterial analytes compared to CFUmL. 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 FilmArray 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 FilmArray 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.

The FilmArray Pneumonia (PN) Panel is designed to simultaneously identify 26 potential pathogens of lower respiratory tract infection (LRTI) and associated antimicrobial resistance (AMR) genes from a sputum-like (induced and expectorated sputum as well as endotracheal aspirate, ETA) or bronchoalveolar lavage (BAL)-like (BAL and mini-BAL) specimens obtained from individuals with signs and/or symptoms of lower respiratory tract infection in a time (~1 hour) that allows the test results to be used in determining appropriate patient treatment and management. FilmArray PN Panel is compatible with BioFire Diagnostics' (BioFire) PCR-based in vitro diagnostic FilmArray 2.0 (K143178) and FilmArray Torch (K160068) systems for infectious disease testing. A specific software module (i.e. FilmArray PN Panel pouch module) is used to perform FilmArray PN Panel testing on these systems.

Bacteria - Quantitative Results: 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
Bacteria (Atypical) - Qualitative Results: Chlamydia pneumoniae, Legionella pneumophila, Mycoplasma pneumoniae
Antimicrobial Resistance Genes: blaCTX-M (Extended spectrum beta-lactamase (ESBL)), blaIMP (Carbapenem resistance), blaKPC (Carbapenem resistance), mecA/mecC and MREJ (Methicillin resistance), blaNDM (Carbapenem resistance), blaOXA48-like (Carbapenem resistance), blaVIM (Carbapenem resistance)
Viruses: Adenovirus, Coronavirus, Human Metapneumovirus, Human Rhinovirus/Enterovirus, Influenza A, Influenza B, Parainfluenza Virus, Respiratory Syncytial Virus

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

The FilmArray instrument contains a coordinated system of inflatable bladders and seal points, which act on the pouch to control the movement of liquid between the pouch blisters. When a bladder is inflated over a reagent blister, it forces liquid from the blister into connecting channels. Alternatively, when a seal is placed over a connecting channel it acts as a valve to open or close a channel. In addition, electronically controlled pneumatic pistons are positioned over multiple plungers in order to deliver the rehydrated reagents into the blisters at the appropriate times. Two Peltier devices control heating and cooling of the pouch to drive the PCR reactions and the melt curve analysis.

Nucleic acid extraction occurs within the FilmArray pouch using mechanical and chemical lysis followed by purification using standard magnetic bead technology. After extracting and purifying nucleic acids from the unprocessed sample, the FilmArray performs a nested multiplex PCR that is executed in two stages. During the first stage, the FilmArray performs a single, large volume, highly multiplexed reverse transcription PCR (rt-PCR) reaction. The products from first stage PCR are then diluted and combined with a fresh, primer-free master mix and a fluorescent double stranded DNA binding dye (LC Green® Plus, BioFire Diagnostics). The solution is then distributed to each well of the array. Array wells contain sets of primers designed specifically to amplify sequences internal to the PCR products generated during the first stage PCR reaction. The 2nd stage PCR, or nested PCR, is performed in single plex fashion in each well of the array. At the conclusion of the 2nd stage PCR, the array is interrogated by melt curve analysis for the detection of signature amplicons denoting the presence of specific targets. A digital camera placed in front of the 2nd stage PCR captures fluorescent images of the PCR reactions and software interprets the data.

The FilmArray Software automatically interprets the results of each DNA melt curve analysis and combines the data with the results of the internal pouch controls to provide a test result for each organism on the panel.

A feature of the FilmArray PN Panel is the reporting of organism abundance for common bacteria in discrete bins representing 10^4, 10^5, 10^6, and >10^7 genomic copies/mL. The panel accomplishes this by comparing the amplification of the bacterial assays with that of a Quantified Standard Material (QSM) present in the pouch.

Here's an analysis of the provided text regarding the FilmArray Pneumonia Panel, focusing on the acceptance criteria and study details. It's important to note that this document is a Special 510(k) Summary for a labeling modification related to a previously cleared device. Therefore, it primarily discusses the change and its impact on the device's labeling, rather than presenting a comprehensive de novo validation study.

Key takeaway: The document describes a labeling modification due to a stability issue with the Adenovirus2 assay (specifically for Adenovirus C) within 6 months of the pouch expiration date. It does not provide details of an initial, full validation study with acceptance criteria and reported performance for all analytes, as that would have been part of the original K180966 submission. The information below is extracted from what's available in this specific document regarding the impact of the noted issue.

1. Table of Acceptance Criteria and Reported Device Performance

This document does not present a table of general acceptance criteria and reported performance for all analytes of the FilmArray Pneumonia Panel since it's a labeling modification submission. The focus is specifically on the change in performance for Adenovirus C due to stability.

The "acceptance criteria" discussed here are essentially the observed degradation in sensitivity and the resulting limitation on the use of the device for Adenovirus C detection under specific conditions.

Note: The original acceptance criteria for the initial clearance (K180966) would have included specific sensitivity (Limit of Detection - LoD) and specificity targets, which are not detailed in this specific document.

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

The document does not specify a "test set" in the context of a de novo validation study. Instead, it refers to a stability study where the issue with Adenovirus2 assay's performance was discovered.

• Sample Size for Test Set: Not explicitly stated as a separate test set. The issue was identified during a stability study of the device pouches.
• Data Provenance: The issue was identified through internal stability study results conducted by BioFire Diagnostics, LLC. No country of origin for clinical samples is mentioned, as the data appears to be from analytical testing (stability of laboratory-manufactured pouches). The study type is retrospective in the sense that previously manufactured pouches were being tested for stability over time.

3. Number of Experts Used to Establish Ground Truth and Qualifications

Not applicable. This document does not describe a study involving expert consensus to establish ground truth for clinical cases. The issue identified was an analytical performance degradation discovered during internal stability testing.

4. Adjudication Method

Not applicable. This document is not describing a study that required adjudication of complex clinical cases or image interpretations. The "adjudication" was the internal assessment of stability study results and the determination that the performance characteristic (LoD for Adenovirus C) had degraded under specific conditions.

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

Not applicable. The device is an in vitro diagnostic (IVD) based on molecular detection, not one requiring human interpretation of results. Therefore, an MRMC study is not relevant to this type of device.

6. Standalone (Algorithm Only) Performance

Yes, the information presented relates to standalone performance of the device. The reported impairment in LoD for Adenovirus C was determined through analytical testing of the device itself (the assay in the pouch) under specific storage conditions. There is no human-in-the-loop component in the detection process of the FilmArray Pneumonia Panel.

7. Type of Ground Truth Used

The ground truth used for identifying this issue was analytical performance data (stability study results) and the degradation of the Limit of Detection (LoD) for Adenovirus C, which represents a quantifiable measure of the assay's sensitivity. This is akin to a "spike-in" experiment or testing known positive controls at various concentrations across the shelf-life of the product.

8. Sample Size for the Training Set

Not applicable. This document describes a stability issue with an already-cleared device and a subsequent labeling modification. It does not refer to a "training set" in the context of an algorithm or AI development. The device pre-dates common AI/ML nomenclature in medical device submissions for IVDs.

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

Not applicable, as there is no "training set" described in this document.

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