FilmArray Pneumonia Panel plus

K181324 · Biofire Diagnostics, LLC · QDS · Nov 15, 2018 · Pathology

Device Facts

Record IDK181324
Device NameFilmArray Pneumonia Panel plus
ApplicantBiofire Diagnostics, LLC
Product CodeQDS · Pathology
Decision DateNov 15, 2018
DecisionSESE
Submission TypeTraditional
Regulation21 CFR 866.4001
Device ClassClass 2
AttributesReal-World Evidence

Real-World Evidence

SubmissionDeviceSponsorRWD SourcesRWE Use SummaryKey Tags
K181324 · Nov 15, 2018FilmArray Pneumonia Panel plusBiofire Diagnostics, LLCResidual clinical specimens (BAL and sputum) from routine clinical careResidual clinical specimens were used to establish the clinical performance (sensitivity/specificity) of the FilmArray Pneumonia Panel plus in a multi-center prospective study.Residual clinical specimens; Clinical performance; Prospective clinical study

Clinical Evidence

Study DesignPopulationComparatorKey Endpoints
Prospective clinical study; Multi-center prospective study; Follow-up/Duration: October 2016 to July 2017; Study Period: October 2016 to July 2017Individuals meeting MERS-CoV clinical and/or epidemiological criteria; Sample Size: 1764 (final data set of 846 BAL and 836 sputum specimens); Number of Sites: 8Quantitative reference culture (qRefCx) and PCR/sequencing-based comparator methodsPositive Percent Agreement (PPA) and Negative Percent Agreement (NPA) for viral and bacterial analytes

Indications for Use

The FilmArray® Pneumonia Panel plus is a multiplexed nucleic acid test intended for use with FilmArray®, FilmArray® 2.0, or FilmArray® Torch systems for the simultaneous detection 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) obtained from individuals meeting MERS-CoV clinical and/or epidemiological criteria. Testing with FilmArray Pneumonia Panel plus should not be performed unless the patient meets clinical and/or epidemiologic criteria for testing suspecimens. 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, 10^6, 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: 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 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.

Device Story

Multiplexed nucleic acid test for lower respiratory tract infection (LRTI) pathogens; inputs: sputum-like or BAL-like specimens; process: mechanical/chemical lysis, magnetic bead purification, nested multiplex PCR (two-stage), melt curve analysis; outputs: qualitative detection of MERS-CoV, atypical bacteria, viruses, AMR genes; semi-quantitative binning (10^4 to ≥10^7 copies/mL) for common bacteria; used in clinical labs with FilmArray 2.0/Torch systems; results aid differential diagnosis of MERS-CoV and LRTI; clinical decision-making supported by pathogen identification and relative abundance estimation; benefits: rapid (~1 hour) identification of pathogens and resistance markers to guide treatment.

Clinical Evidence

Prospective multi-center study (846 BAL, 836 sputum specimens) compared device to quantitative reference culture (qRefCx) and PCR/sequencing. Sensitivity/PPA and specificity/NPA calculated for all analytes. Additional archived and contrived specimen studies supplemented data for rare analytes and MERS-CoV. Performance met predefined acceptance criteria.

Technological Characteristics

Multiplex nucleic acid detection; nested PCR; melt curve analysis; automated interpretation; room temperature reagent storage; compatible with FilmArray, 2.0, and Torch systems; software-based result generation; semi-quantitative binning via Quantified Standard Material (QSM).

Indications for Use

Indicated for simultaneous detection/identification of MERS-CoV, respiratory viral/bacterial pathogens, and select antimicrobial resistance genes in sputum-like or BAL-like specimens from patients meeting MERS-CoV clinical/epidemiological criteria.

Regulatory Classification

Identification

A multiplex respiratory panel to detect and identify emerging respiratory pathogen(s) and common respiratory pathogens in human clinical specimens is identified as an in vitro diagnostic device intended for the qualitative detection and identification of both emerging and common respiratory pathogens from individuals meeting specific emerging respiratory pathogen clinical and/or epidemiological criteria. For example, clinical signs and symptoms associated with infection of the emerging respiratory pathogen, contact with a probable or confirmed emerging respiratory pathogen case, history of travel to geographic locations where cases of the emerging respiratory pathogen were detected, or other epidemiological links for which testing of the emerging respiratory pathogen may be indicated. A device to detect and identify emerging respiratory pathogen(s) and common respiratory pathogens in human clinical specimens, and in turn to distinguish emerging respiratory pathogen(s) from common respiratory pathogens, is intended to aid in the differential diagnosis of the emerging respiratory pathogen infection, in conjunction with other clinical, epidemiologic, and laboratory data, in accordance with the guidelines provided by the appropriate public health authorities.

Special Controls

*Classification.* Class II (special controls). The special controls for this device are:(1) The intended use for the labeling required under § 809.10 of this chapter must include a description of what the device detects and measures, the specimen types, the results provided to the user, the clinical indications for which the test is to be used, the specific intended population(s), the testing location(s) where the device is to be used (if applicable), and other conditions of use as appropriate. (2) The labeling required under § 809.10 of this chapter must include: (i) A device description, including the parts that make up the device, ancillary reagents required but not provided, and an explanation of the methodology. (ii) Performance characteristics from analytical studies, including cut-off (if applicable), analytical sensitivity ( *i.e.,* limit of detection), inclusivity, reproducibility, interference, cross-reactivity, instrument carryover/cross-contamination (if applicable), and specimen stability.(iii) Detailed instructions for minimizing the risk of potential users' exposure to the emerging respiratory pathogen(s) that may be present in test specimens and those used as control materials. (iv) Detailed instructions for minimizing the risk of generating false positive test results due to carry-over contamination from positive test specimens and/or positive control materials. (v) A warning statement that the interpretation of test results requires experienced healthcare professionals who have training in principles and use of infectious disease diagnostics and reporting of results, in conjunction with the patient's medical history, clinical signs and symptoms, and the results of other diagnostic tests. (vi) A warning statement that culture should not be attempted in cases of positive results for an emerging respiratory pathogen unless a facility with an appropriate level of laboratory biosafety ( *e.g.,* BSL 3 and BSL 3+) is available to receive and culture specimens.(vii) A warning statement that device positive results for one or more common respiratory pathogens do not rule out bacterial infection, or co-infection with other common respiratory pathogens. (viii) A warning statement that respiratory pathogen(s) detected may not be the definite cause of disease. (ix) A warning statement that the use of additional laboratory testing ( *e.g.* bacterial culture, immunofluorescence, x-ray findings) and clinical presentation must be taken into consideration in order to obtain the final diagnosis of a respiratory infection.(x) A limiting statement that device negative results for the common respiratory pathogens do not preclude infection of a respiratory pathogen and should not be used as the sole basis for diagnosis, treatment, or other patient management decisions. (xi) A limiting statement that analyte targets ( *e.g.,* pathogen nucleic acid sequences or other molecular signatures) may persist in vivo, independent of organism viability. Detection of analyte target(s) does not imply that the corresponding pathogen(s) is infectious, nor is the causative agent(s) for clinical symptoms.(xii) A limiting statement that detection of pathogen nucleic acid sequences or other molecular signatures is dependent upon proper specimen collection, handling, transportation, storage and preparation. Failure to observe proper procedures in any one of these steps can lead to incorrect results. There is a risk of false negative values resulting from improperly collected, transported, or handled specimens. (xiii) A limiting statement that there is a risk of false positive values resulting from cross-contamination by target organisms, their nucleic acids or amplified product, or from non-specific signals in the assay. (xiv) A limiting statement that there is a risk of false negative results due to the presence of nucleic acid sequence variants in the pathogen targets of the device. (xv) A limiting statement that device performance was not established in immunocompromised patients. (xvi) A limiting statement that positive and negative predictive values are highly dependent on prevalence. The device performance was established during one or more specific respiratory seasons. The performance for some respiratory pathogens may vary depending on the prevalence and patient population tested. False positive test results are likely when prevalence of disease due to a particular respiratory pathogen is low or non-existent in a community. (xvii) In situations where the performance of the device was estimated based largely on testing pre-selected banked retrospective clinical specimens and/or contrived clinical specimen, a limiting statement that the estimated device performance of that specific pathogen or pathogen subtype may not reflect the performance or prevalence in the intended use population. (xviii) For devices with an intended use that includes detection of emerging respiratory pathogen(s), a limiting statement that testing with the device should not be performed unless the patient meets clinical and/or epidemiologic criteria for testing suspected specimens of the emerging respiratory pathogen. (xix) For devices with an intended use that includes detection of emerging respiratory pathogen(s), a limiting statement that positive results obtained with the device for the emerging respiratory pathogen are for the presumptive identification of that pathogen and that the definitive identification of the emerging respiratory pathogen requires additional testing and confirmation procedures in consultation with the appropriate public health authorities ( *e.g.,* local or state public health departments) for whom reporting is necessary.(xx) For devices with an intended use that includes detection of emerging respiratory pathogen(s), a limiting statement that negative results for the emerging respiratory pathogen, even in the context of device positive results for one or more of the common respiratory pathogens, do not preclude infection with the emerging respiratory pathogen and should not be used as the sole basis for patient management decisions. (xxi) For devices with an intended use that includes detection of emerging respiratory pathogen(s), a limiting statement that negative results for the emerging respiratory pathogen may be due to infection of the emerging respiratory pathogen at a specific respiratory tract location that may not be detected by a particular clinical specimen type. A negative result for the emerging respiratory pathogen in an asymptomatic individual does not rule out the possibility of future illness and does not demonstrate that the individual is not infectious. (xxii) For devices with an intended use that includes detection of emerging respiratory pathogen(s), a limiting statement that a nationally notifiable Rare Disease of Public Health Significance caused by an emerging respiratory pathogen must be reported, as appropriate, to public health authorities in accordance with local, state, and federal law. (3) Design verification and validation must include: (i) Performance results of an appropriate clinical study ( *e.g.,* a prospective clinical study) for each specimen type, and, if appropriate, results from additional characterized samples. The clinical study must be performed on a study population consistent with the intended use population and must compare the device performance to results obtained using FDA-accepted comparator methods or to expected negative results if the infection is not generally expected in the intended use population. Clinical specimens evaluated in the study must contain relevant organism concentrations applicable to the specimen type(s) and the targeted analyte(s). Detailed documentation must be kept of that study and its results, including the study protocol, study report for the proposed intended use, testing results, and results of all statistical analyses.(ii) For devices with an intended use that includes detection of emerging respiratory pathogen(s) for which an FDA recommended panel is available, design verification and validation must include the performance results of an analytical study testing an FDA recommended reference panel of characterized samples that contain the emerging respiratory pathogen. Detailed documentation must be kept of that study and its results, including the study protocol, study report for the proposed intended use, testing results, and results of all statistical analyses. (iii) An appropriate risk mitigation strategy, including a detailed description of all procedures and methods, for the post-market identification of genetic mutations and/or novel respiratory pathogen isolates or strains ( *e.g.,* regular review of published literature and annual in silico analysis of target sequences to detect possible mismatches. The required documentation for this device must also include all of the results, including any findings, from the application of this post-market mitigation strategy.(iv) For devices with an intended use that includes detection of multiple common respiratory pathogens, in addition to detecting emerging respiratory pathogen(s) in human clinical specimens, a detailed description of the identity, phylogenetic relationship, or other recognized characterization of the common respiratory pathogens that the device is designed to detect is addressed. Also, address in detail how the device results might be used in a diagnostic algorithm and other measures that might be needed for a laboratory diagnosis of respiratory tract infection. Perform an evaluation of the device compared to a currently appropriate and FDA accepted comparator method. Detailed documentation must be kept of that study and its results, including the study protocol, study report for the proposed intended use, testing results, and results of all statistical analyses. (v) A detailed device description, including the parts that make up the device, ancillary reagents required but not provided, and a detailed explanation of the methodology, including molecular target(s) for each analyte, design of target detection reagents, rationale for target selection, limiting factors of the device ( *e.g.,* saturation level of hybridization and maximum amplification and detection cycle number), internal and external controls, and computational path from collected raw data to reported result (*e.g.,* how collected raw signals are converted into a reported signal and result), as applicable and appropriate.(vi) A detailed description of the device software, including software applications and hardware-based devices that incorporate software. (vii) For devices with an intended use that includes detection of Influenza A and Influenza B viruses and/or detection and differentiate between the Influenza A virus subtypes in human clinical specimens, in addition to detecting emerging respiratory pathogen(s), a detailed description of the identity, phylogenetic relationship, or other recognized characterization of the Influenza A and B viruses that the device is designed to detect, a description of how the device results might be used in a diagnostic algorithm and other measures that might be needed for a laboratory identification of Influenza A or B virus and of specific Influenza A virus subtypes, and a description of the clinical and epidemiological parameters that are relevant to a patient case diagnosis of Influenza A or B and of specific Influenza A virus subtypes. Perform an evaluation of the device compared to a currently appropriate and FDA accepted comparator method. Detailed documentation must be kept of that study and its results, including the study protocol, study report for the proposed intended use, testing results, and results of all statistical analyses. (4) For devices with an intended use that includes detection of Influenza A and Influenza B viruses and/or detection and differentiate between the Influenza A virus subtypes in human clinical specimens, in addition to detecting emerging respiratory pathogen(s), the labeling required under § 809.10 of this chapter must include the following: (i) Where applicable, a limiting statement that performance characteristics for Influenza A were established when Influenza A/H3 and A/H1-2009 (or other pertinent Influenza A subtypes) were the predominant Influenza A viruses in circulation. When other Influenza A viruses are emerging, performance characteristics may vary. (ii) Where applicable, a warning statement that reads if infection with a novel Influenza A virus is suspected based on current clinical and epidemiological screening criteria recommended by public health authorities, specimens should be collected with appropriate infection control precautions for novel virulent influenza viruses and sent to state or local health departments for testing. Viral culture should not be attempted in these cases unless a BSL 3+ facility is available to receive and culture specimens. (iii) Where the device results interpretation involves combining the outputs of several targets to get the final results, such as a device that both detects Influenza A and differentiates all known Influenza A subtypes that are currently circulating, the device's labeling required under § 809.10(b)(9) of this chapter must include a clear interpretation instruction for all valid and invalid output combinations, and recommendations for any required follow up actions or retesting in the case of an unusual or unexpected device result. (iv) A limiting statement that if a specimen yields a positive result for Influenza A, but produces negative test results for all specific influenza A subtypes intended to be differentiated ( *e.g.,* H1-2009 and H3), this result requires notification of appropriate local, state, or federal public health authorities to determine necessary measures for verification and to further determine whether the specimen represents a novel strain of Influenza A.(5) The manufacturer must perform annual analytical reactivity testing of the device with contemporary influenza strains. This annual analytical reactivity testing must meet the following criteria: (i) The appropriate strains to be tested will be identified by FDA in consultation with the Centers for Disease Control and Prevention (CDC) and sourced from CDC or an FDA designated source. If the annual strains are not available from CDC, FDA will identify an alternative source for obtaining the requisite strains. (ii) The testing must be conducted according to a standardized protocol considered and determined by FDA to be acceptable and appropriate. (iii) By July 31 of each calendar year, the results of the last 3 years of annual analytical reactivity testing must be included as part of the device's labeling. If a device has not been on the market long enough for 3 years of annual analytical reactivity testing to have been conducted since the device received marketing authorization from FDA, then the results of every annual analytical reactivity testing since the device received marketing authorization from FDA must be included. The results must be presented as part of the device's labeling in a tabular format, which includes the detailed information for each virus tested as described in the certificate of authentication, either by: (A) Placing the results directly in the device's labeling required under § 809.10(b) of this chapter that physically accompanies the device in a separate section of the labeling where the analytical reactivity testing data can be found; or (B) In the device's label or in other labeling that physically accompanies the device, prominently providing a hyperlink to the manufacturer's public website where the analytical reactivity testing data can be found. The manufacturer's home page, as well as the primary part of the manufacturer's website that discusses the device, must provide a prominently placed hyperlink to the web page containing this information and must allow unrestricted viewing access. (6) If one of the actions listed at section 564(b)(1)(A)-(D) of the FD&C Act occurs with respect to an influenza viral strain, or if the Secretary of Health and Human Services (HHS) determines, under section 319(a) of the Public Health Service Act, that a disease or disorder presents a public health emergency, or that a public health emergency otherwise exists, with respect to an influenza viral strain: (i) Within 30 days from the date that FDA notifies manufacturers that characterized viral samples are available for test evaluation, the manufacturer must have testing performed on the device with those viral samples in accordance with a standardized protocol considered and determined by FDA to be acceptable and appropriate. The procedure and location of testing may depend on the nature of the emerging virus. (ii) Within 60 days from the date that FDA notifies manufacturers that characterized viral samples are available for test evaluation and continuing until 3 years from that date, the results of the influenza emergency analytical reactivity testing, including the detailed information for the virus tested as described in the certificate of authentication, must be included as part of the device's labeling in a tabular format, either by: (A) Placing the results directly in the device's labeling required under § 809.10(b) of this chapter that physically accompanies the device in a separate section of the labeling where analytical reactivity testing data can be found, but separate from the annual analytical reactivity testing results; or (B) In a section of the device's label or in other labeling that physically accompanies the device, prominently providing a hyperlink to the manufacturer's public website where the analytical reactivity testing data can be found. The manufacturer's home page, as well as the primary part of the manufacturer's website that discusses the device, must provide a prominently placed hyperlink to the web page containing this information and must allow unrestricted viewing access.

Predicate Devices

Submission Summary (Full Text)

{0} # 510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY A. 510(k) Number: K181324 B. Purpose for Submission: To obtain a substantial equivalence determination for the FilmArray Pneumonia Panel plus C. Measurands: 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, Chlamydia pneumoniae, Legionella pneumophila, Mycoplasma pneumoniae, Adenovirus, Coronavirus, Human Metapneumovirus, Human Rhinovirus/Enterovirus, Influenza A, Influenza B, Middle East Respiratory Syndrome Coronavirus (MERS-CoV), Parainfluenza Virus, Respiratory Syncytial Virus, CTX-M, IMP, KPC, NDM, OXA-48-like, VIM, mecA/C and MREJ. D. Type of Test: Qualitative and quantitative nucleic acid amplification assay E. Applicant: BioFire Diagnostics, LLC F. Proprietary and Established Names: FilmArray Pneumonia Panel plus G. Regulatory Information: 1. Regulation section: 21 CFR 866.4001 – MERS-CoV and common respiratory pathogens multiplex nucleic acid detection system 2. Classification: Class II (Special Controls) 3. Product code: PZF {1} #### 4. Panel: 83-Microbiology ### H. Indications for use: #### 1. Indications for use(s): The FilmArray Pneumonia Panel plus is a multiplexed nucleic acid test intended for use with FilmArray, FilmArray 2.0, or FilmArray 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 FilmArray 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-qualitatively with bins representing approximately \( 10^{4} \) , \( 10^{5} \) , \( 10^{6} \) , or \( \geq10^{7} \) 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 \( \geq 10^{7} \) 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: 2 {2} | Atypical Bacteria | | | | --- | --- | --- | | *Chlamydia pneumoniae* | *Legionella pneumophila* | *Mycoplasma pneumoniae* | | Viruses | | | | Middle East Respiratory Syndrome Coronavirus | | | | Adenovirus | Human Rhinovirus/Enterovirus | Parainfluenza Virus | | Coronavirus | Influenza A | Respiratory Syncytial Virus | | Human Metapneumovirus | Influenza B | | | Antimicrobial Resistance Genes | | | | CTX-M | NDM | *mecA/C* and MREJ | | IMP | OXA-48-like | | | KPC | VIM | | 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. FilmArray 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. FilmArray Pneumonia Panel *plus* MERS-CoV negative results, even in the context of a FilmArray 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 FilmArray 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 FilmArray 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) 3 {3} detected by the FilmArray 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 FilmArray 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 FilmArray 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 FilmArray Pneumonia Panel plus, to further speciate analytes in genus, complex, or group results if desired, to identify bacterial pathogens present below the 10⁴ copies/mL bin if desired, and for antimicrobial susceptibility testing. 2. Indication(s) for use: Same as Intended Use 3. Special conditions for use statement(s): - For prescription use only - For in vitro diagnostic use only 4 {4} # Limitations: - For prescription use only. - The FilmArray Pneumonia Panel plus has not been validated for testing of specimens other than unprocessed sputum-like and BAL-like specimens. - Contact or treatment of specimens with decontaminating agents (bleach, MycoPrep (NaOH and NALC), 2% NaOH and 5% Oxalic acid) can cause false negative results (see Interference section). - The performance of the FilmArray Pneumonia Panel plus has not been established for monitoring treatment of infection. - The effect of antibiotic treatment on test performance including semi-quantitative bin results has not been specifically evaluated. - Viral and bacterial nucleic acids may persist in vivo independent of organism viability. Detection of organism target(s) does not imply that the corresponding organisms are infectious or are the causative agents for clinical symptoms. - The FilmArray Pneumonia Panel plus results for bacteria are provided as a qualitative Detected/Not Detected result with an associated semi-quantitative bin result of 10⁴, 10⁵, 10⁶, or ≥10⁷ copies of genomic nucleic acid per milliliter of specimen. An exact quantitative value is not provided. The semi-quantitative (copies/mL) bin result does not distinguish between nucleic acid from live or dead bacteria. - A negative FilmArray Pneumonia Panel plus result does not exclude the possibility of viral or bacterial infection. Negative test results may occur from the presence of sequence variants in the region targeted by the assay, the presence of inhibitors, technical error, sample mix-up or an infection caused by an organism not detected by the panel. Test results may also be affected by concurrent antiviral/antibacterial therapy or levels of organism in the specimen that are below the limit of detection for the test or below the reportable level for bacterial analytes. Negative results should not be used as the sole basis for diagnosis, treatment, or other patient management decisions. - Concomitant culture of specimens is required with the FilmArray Pneumonia Panel plus. Culture is needed for recovery of isolates and antimicrobial susceptibility testing, as well as further speciation of genus, complex, or group level results (if desired). - Due to the genetic similarity between human rhinovirus and enterovirus, the FilmArray Pneumonia Panel plus cannot reliably differentiate them. A FilmArray Pneumonia Panel plus Human Rhinovirus/Enterovirus Detected result should be followed-up using an alternate method (e.g. cell culture or sequence analysis) if differentiation between the viruses is required. - The in-silico analyses performed to predict amplification and detection of organisms and antimicrobial resistance genes were based on a comparison of target gene sequences available in GenBank to FilmArray Pneumonia Panel plus primer sequences. In-silico analyses were performed between January 2016 and January 2018. Entries of new sequences added to the database after these dates have not been evaluated. Additional limitations on reactivity may be identified as new 5 {5} sequence data are deposited and/or as new sequence variants emerge. - Based on in-silico analysis, the MREJ assay (which is only reported if Staphylococcus aureus is detected and the mecA/C assay is also positive) is predicted to have impaired reactivity or to be non-reactive with MREJ types ix, xv and xviii, as well as types xix and xx (associated with methicillin-sensitive S. aureus; MSSA), and MREJ sequences annotated from non-aureus Staphylococcus species and non-Staphylococci such as Bacillus cereus, Bacillus thuringiensis, Macrococcus caseolyticus, Clostridium acidurici, and Rummeliibacillus stabekisii. - Positive and negative predictive values are highly dependent on prevalence. False negative test results are more likely during peak activity when prevalence of disease is high. False positive test results are more likely during periods when prevalence is moderate to low. - Performance characteristics for influenza A were established during the 2016-2017 influenza season. When other novel influenza A viruses are emerging, performance characteristics may vary. If infection with a novel influenza A virus is suspected based on current clinical and epidemiological screening criteria recommended by public health authorities, specimens should be collected with appropriate infection control precautions for novel virulent influenza viruses and sent to state or local health departments for testing. Viral culture should not be attempted in these cases unless a BSL 3+ facility is available to receive and culture specimens. - Due to the small number of positive specimens collected for certain organisms during the prospective clinical study, performance characteristics for several analytes in one or both matrices were primarily established using archived and/or contrived specimens as detailed in the Clinical Performance section. # 4. Special instrument requirements: The FilmArray Pneumonia Panel plus is performed on FilmArray, FilmArray 2.0, or FilmArray Torch systems. # I. Device Description: 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 FilmArray, FilmArray 2.0, and FilmArray Torch 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 FilmArray pouch and a sputum-like or BAL-like sample mixed with the provided Sample Buffer into the other 6 {6} 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 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 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. # Materials provided in each FilmArray Pneumonia Panel plus kit: Each kit contains sufficient reagents to test 30 samples (30-test kit; RFIT-ASY-0144) or 6 samples (6-test kit; RFIT-ASY-0145): - Individually-packaged FilmArray Pneumonia Panel plus pouches - Single-use (1.0 mL) Sample Buffer ampoules - Single-use pre-filled (1.5 mL) Hydration Injection Vials (blue) - Single-use Sample Injection Vials (red) - Individually-packaged Transfer Pipettes 7 {7} # **Materials required but not provided:** - FilmArray system including: - FilmArray 2.0 or FilmArrayTouch and accompanying software - FilmArray Pouch Loading Station - 10% bleach solution # **Interpretation of Results** When PCR2 is complete, the FilmArray instrument performs a DNA melting analysis on the PCR products and measures the fluorescence signal generated in each well (for more information see appropriate FilmArray Operator's Manual). The FilmArray Software then performs several analyses and assigns a final assay result. The steps in the analyses are described below. # Analysis of Melt Curves The FilmArray Software evaluates the DNA melt curve for each well of the PCR2 array to determine if a PCR product was present in that well. If the melt profile indicates the presence of a PCR product, then the analysis software calculates the melting temperature (Tm) of the curve and compares it against the expected Tm range for the assay. If the software determines that the Tm of the curve is within the assay-specific Tm range, the melt curve is called positive. If the software determines that the Tm of the curve is not in the appropriate Tm range, the melt curve is called negative. # Analysis of Replicates Once positive melt curves have been identified, the software evaluates the replicates for each assay to determine the assay result. For an assay to be called positive, two associated melt curves must be called positive, and both Tms must be similar. Assays that do not meet these criteria are called negative. # Analysis of Assay Results for Bacteria The assays in the FilmArray Pneumonia Panel plus for detection of bacteria that are reported semi-quantitatively are designed to amplify genes that are present in single copies within the chromosome of the target bacterium and are used to estimate genomic copies of bacterial nucleic acid per milliliter (copies/mL) of specimen. The FilmArray Software calculates an approximate value for each gene target based on real-time PCR amplification data relative to the QSM (internal reference of known quantity). Assays with no measurable amplification or a value below 10³·⁵ copies/mL are called negative. Assays with a value equal to or greater than 10³·⁵ copies/mL are called positive. 8 {8} # Organism and Antimicrobial Resistance Gene Interpretation Each positive and negative assay result is interpreted by the FilmArray Software to provide results for the identification of specific bacteria, atypical bacteria, viruses, and antimicrobial resistance (AMR) genes as shown in the Table below. For most analytes detected by the FilmArray Pneumonia Panel plus, interpretations are based on the result of a single assay. However, results for MERS-CoV, Staphylococcus aureus, Adenovirus, and the AMR genes require interpretation based on more than one assay result, as discussed in the relevant sections below. | MERS-CoV – Qualitative Results | | | --- | --- | | Middle East Respiratory Syndrome Coronavirus | | | Other Common Lower Respiratory Pathogens | | | Bacteria – Quantitative Results | Antimicrobial Resistance Genes | | Acinetobacter calcoaceticus-baumannii complex | blaCTX-M (Extended spectrum beta-lactamase | | Enterobacter cloacae complex | blaIMP (Carbapenem resistance) | | Escherichia coli | blaKPC (Carbapenem resistance) | | Haemophilus influenzae | mecA/mecC and MREJ (Methicillin resistance) | | Klebsiella aerogene | blaNDM (Carbapenem resistance) | | Klebsiella oxytoca | blaOxa48-like (Carbapenem resistance) | | Klebsiella pneumoniae group | blaVIM (Carbapenem resistance) | | Moraxella catarrhalis | Viruses | | Proteus spp. | Adenovirus | | Pseudomonas aeruginosa | Coronavirus | | Serratia marcescens | Human Metapneumovirus | | Streptococcus agalactiae | Human Rhinovirus/Enterovirus | | Streptococcus pneumoniae | Influenza A | | Streptococcus pyogenes | Influenza B | | Bacteria (Atypical) - Qualitative Results | Parainfluenza Virus | | Chlamydia pneumoniae | Respiratory Syncytial Virus | | Legionella pneumophila | | | Mycoplasma pneumoniae | | # Interpretations and Semi-quantitative Bin Results for Bacteria The FilmArray Pneumonia Panel plus provides a Detected or Not Detected result as well as a semi-quantitative bin result ($10^4$ copies/mL, $10^5$ copies/mL, $10^6$ copies/mL or $\geq 10^7$ copies/mL) for most bacteria. The bin result represents the approximate number of specific bacterial genomes in the specimen and is intended to provide a simple assessment of relative quantities of different bacteria in a lower respiratory specimen based on a molecular method. For bacteria, negative assays (no measurable amplification or value less than $10^{3.5}$ copies/mL) are reported as Not Detected. Positive assays are reported as Detected 9 {9} and a bin result is assigned based on the assay value. Each bin is defined by discrete upper and lower limits spanning a 1-log range of values (see Table 1) such that the bin result reflects the assay value within the nearest ±0.5-log. Table 1: FilmArray Pneumonia Panel plus Bin Results for Bacteria | Assay Result | | Reported Result and Bin Result | | | --- | --- | --- | --- | | Negative OR | <10^{3.5} copies/mL | Not Detected | | | Positive AND | ≥10^{3.5} – <10^{4.5} copies/mL | Detected | 10^{4} copies/mL | | Positive AND | ≥10^{4.5} – <10^{5.5} copies/mL | Detected | 10^{5} copies/mL | | Positive AND | ≥10^{5.5} – <10^{6.5} copies/mL | Detected | 10^{6} copies/mLD | | Positive AND | ≥10^{6.5} copies/mL | Detected | ≥10^{7} copies/mL | # Staphylococcus aureus The FilmArray Pneumonia Panel plus pouch contains two different assays (Saureus1 and Saureus2) for the detection of Staphylococcus aureus. The FilmArray Software interprets each of these assays independently (as described above) and if one or a combination of the assays is positive, the result will be Staphylococcus aureus Detected with the appropriate bin result. If both assays are negative the result will be Staphylococcus aureus Not Detected. # Interpretations for Atypical Bacteria and Viruses Results for most Atypical Bacteria and Viruses are reported qualitatively as Detected or Not Detected based on an individual corresponding assay result. If the assay is positive the result will be Detected, and if the assay is negative, the result will be Not Detected. # Adenovirus The FilmArray Pneumonia Panel plus pouch contains three different assays (Adenovirus2, Adenovirus3, and Adenovirus7). The FilmArray Software interprets each of these assays independently (as described above) and the results are combined as a final result for the virus. If one or any combination of assays is positive, the result will be Adenovirus Detected. If all assays are negative, the result will be Adenovirus Not Detected. # Middle East Respiratory Syndrome Coronavirus The FilmArray Pneumonia Panel plus pouch contains two different assays (MERS1 and MERS2) for the detection of Middle East Respiratory Syndrome 10 {10} Coronavirus. The FilmArray Software requires both assays to exhibit amplification to report a positive result. If only one MERS assay is positive, the software reports an equivocal result and the sample must be retested. If all assays are negative, the result will be MERS-CoV Not Detected. ## Interpretations for Antimicrobial Resistance (AMR) Genes Results for AMR genes are also reported qualitatively (Detected/Not Detected) based on corresponding assays, but only if an applicable bacterium (i.e. potential carriers of the AMR gene; Table 2) is also detected (≥10³·⁵ copies/mL) in the sample. The results for each of the antimicrobial resistance genes will be listed as either: - Detected – when an applicable bacterium is detected AND the antimicrobial resistance gene assay(s) are positive. - Not Detected – when an applicable bacterium is detected AND the antimicrobial resistance gene assay(s) are negative. - N/A – when all applicable bacteria are Not Detected, regardless of the result for the antimicrobial resistance gene assay(s). Table 2: Antimicrobial Resistance (AMR) Genes and Applicable Organisms | AMR Gene Result | Applicable Bacteria | | --- | --- | | mecA/C and MREJ | Staphylococcus aureus | | CTX-M IMP KPC NDM VIM | Acinetobacter calcoaceticus-baumannii complex Enterobacter cloacae complex Escherichia coli Klebsiella aerogenes Klebsiella oxytoca Klebsiella pneumoniae group Proteus spp. Pseudomonas aeruginosa Serratia marcescens | | OXA-48-like | Enterobacter cloacae complex Escherichia coli Klebsiella aerogenes Klebsiella oxytoca Klebsiella pneumoniae group Proteus spp. Serratia marcescens | Each AMR gene result is associated with a single corresponding assay except for the mecA/C and MREJ result, which is dependent on both the mecA/C assay and the 11 {11} MREJ assay. Detection of both Staphylococcus aureus and the mecA/C and MREJ markers is indicative of Methicillin Resistant Staphylococcus Aureus (MRSA). ## Run Information The Run Information section is displayed at the top of both pages of the test report. It provides information about the sample and the run including: Sample ID, Protocol (sample type), pouch information (Pouch Type, Lot Number, and Serial Number), Run Date, Run Status (Completed, Incomplete, Aborted, Instrument Error, Instrument Communication Error, or Software Error), , the identity of the operator who performed the test, and the instrument used to perform the test. Control results are reported as Passed, Failed, or Invalid. The Table 3 below provides additional information for each of the possible control field results. Table 3: Interpretation of Controls Field on the FilmArray Pneumonia Panel plus Test Report | Control Result | Explanation | Action | | --- | --- | --- | | Passed | The run was successfully completed AND Both pouch controls were successful. | None Report the results provided on the test report. | | Failed | The run was completed BUT At least one of the pouch controls (RNA Process Control and/or QSM) failed. | Repeat the test using a new pouch. If the error persists, contact Customer Technical Support for further instruction. | | Invalid | The controls are invalid because the run did not complete. (Typically this indicates a software or hardware error). | Note any error codes displayed during the run and the Run Status field in the Run Information section of the report. Refer to the appropriate FilmArray Operator's Manual or contact Customer Technical Support for further instruction. Once the error is resolved, repeat the test or repeat the test using another instrument. | ## Detection Summary The Detection Summary section is displayed on the first page of the report and lists the Detected results under each category (Bacteria, Antimicrobial Resistance Genes, Atypical Bacteria, and Viruses), including the semi-quantitative 'Bin (copies/mL)' results for Bacteria. If there are no Detected results in a specific category, the result shown is Detected: None. 12 {12} ## Result Summary The Results Summary is displayed on the second page of the report and provides a full list of test results for each organism and antimicrobial resistance gene including the 'Bin (copies/mL)' result for Bacteria. Possible results for each organism are Detected, Not Detected, Invalid, and N/A. The Table provides an explanation for each interpretation and any follow-up necessary to obtain a final result. Table 4: Reporting of Results and Required Actions | Result | Explanation | Action | | --- | --- | --- | | Detected | The run was successfully completed AND The pouch controls were successful (Passed) AND The assay(s) for the organism were POSITIVE^{a} | Report results. | | Not Detected | The run was successfully completed AND The pouch controls were successful (Passed) AND The assay(s) for the organism were NEGATIVE^{b} | Report results. | | Invalid | The pouch controls were not successful (Failed) OR The run was not successful (Run Status displayed as: Aborted, Incomplete, Instrument Error or Software Error) | See Table 3 for instruction. | | N/A (Antimicrobial Resistance Genes only | The run was successfully completed AND The pouch controls were successful (Passed) AND The assay(s) for the organism(s) associated with the antimicrobial resistance gene were NEGATIVE so the results of the antimicrobial resistance gene are not applicable to the test results. | Report results. | $^{a}$ For bacteria, the organism calculated value must be greater than or equal to 10$^{3.5}$ copies/mL for the assay to be POSITIVE. $^{b}$ For bacteria, a NEGATIVE assay result may indicate no amplification or amplification with an organism calculated value less than 10$^{3.5}$ copies/mL. ### J. Substantial Equivalence Information: 1. Predicate device name(s): FilmArray Respiratory Panel 2 plus (RP2plus) 2. Predicate 510(k) number(s): DEN170017 13 {13} # 3. Comparison with predicate: | Similarities | | | | --- | --- | --- | | Item | New Device: FilmArray Pneumonia Panel *plus* (K181324) | Predicate: FilmArray Respiratory Panel 2 *plus* (DEN170017) | | Indication for Use | The FilmArray Pneumonia Panel *plus* is a multiplexed nucleic acid test intended for use with FilmArray, FilmArray 2.0, or FilmArray Torch systems for the simultaneous detection and identification 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 meeting MERS-CoV clinical and/or epidemiological criteria. Testing with FilmArray 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-qualitatively with bins representing approximately 10^{4}, 10^{5}, 10^{6}, 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* Atypical Bacteria: *Chlamydia pneumoniae*, *Legionella pneumophila*, *Mycoplasma pneumoniae* Antimicrobial Resistance Genes: CTX-M, IMP, KPC, mecA/C + MREJ, NDM, Oxa48-like, VIM Viruses: Adenovirus, Coronavirus, Human Metapneumovirus, Human Rhinovirus/Enterovirus, Influenza A, Influenza B, Middle East Respiratory Syndrome Coronavirus, Parainfluenza virus, | The FilmArray Respiratory Panel 2 *plus* (RP2*plus*) is a multiplexed nucleic acid test intended for use with FilmArray 2.0 or FilmArray Torch systems for the simultaneous qualitative detection and identification of nucleic acids from Middle East Respiratory Syndrome Coronavirus (MERS-CoV) and multiple common viral and bacterial respiratory pathogens in nasopharyngeal swabs (NPS) obtained from individuals meeting MERS-CoV clinical and/or epidemiological criteria. Testing with the FilmArray RP2*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 detection and identification of specific viral and bacterial nucleic acids from MERS-CoV and other respiratory pathogens in 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. FilmArray RP2*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. FilmArray RP2*plus* MERS-CoV negative results, even in the context of a FilmArray RP2*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 NPS specimens from individuals with early infection and from asymptomatic MERS-CoV carriers are not well understood. The FilmArray RP2*plus* MERS-CoV negative results may also be due to lower respiratory tract | 14 {14} | Similarities | | | --- | --- | | Respiratory Syncytial virus 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. FilmArray 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. FilmArray Pneumonia Panel *plus* MERS-CoV negative results, even in the context of a FilmArray 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 FilmArray 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 FilmArray 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^{6} copies/mL bin. Detection of analytes does not rule out co-infection with other organisms: the agent(s) detected by the FilmArray | infection with MERS-CoV that may not be detected by an NPS specimen. In this context, collection of lower respiratory and serum specimens (if possible) for MERS-CoV testing using other laboratory tests is highly recommended in addition to testing for MERS-CoV RNA in NPS specimens (i.e., upper respiratory specimens) using the FilmArray RP2*plus*. A negative FilmArray RP2*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 in the cases of positive FilmArray RP2*plus* results for MERS-CoV unless a BSL 3 facility is available to receive and culture specimens. The following Bacteria and Atypical Bacteria are qualitatively detected by the assay: *Bordetella parapertussis*, *Bordetella pertussis*, *Chlamydia pneumoniae*, *Mycoplasma pneumoniae* Viruses: Adenovirus, Coronavirus, Human Metapneumovirus, Human Rhinovirus/Enterovirus, Influenza A, Influenza B, Middle East Respiratory Syndrome Coronavirus, Parainfluenza Virus, Respiratory Syncytial virus Negative FilmArray RP2*plus* results in the setting of a respiratory illness may be due to infection with pathogens that are not detected by this test, or other pathogens that may not be detected by an NPS specimen. Positive FilmArray RP2*plus* results do not rule out coinfection with other organisms: the agent(s) detected by the FilmArray RP2*plus* may not be the definite cause of disease. Due to the genetic similarity between Human Rhinovirus and Enterovirus, the FilmArray RP2*plus* cannot reliably differentiate them. A positive FilmArray RP2*plus* Rhinovirus/Enterovirus result should be followed up using an alternate method (e.g., cell culture or sequence analysis) if differentiation is required. Performance characteristics for Influenza A were established when Influenza A H1-2009, A H1, and A H3 were the predominant Influenza A viruses in circulation. Performance of detecting Influenza A may vary if other Influenza A strains are circulating or a novel Influenza A virus emerges. If infection with a novel Influenza A virus is suspected based on current clinical and epidemiological screening criteria recommended by public health authorities, specimens should be collected | 15 {15} | Similarities | | | | --- | --- | --- | | | 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 FilmArray 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 FilmArray Pneumonia Panel *plus* results should be used in conjunction with culture results for the determination of 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 *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. | with appropriate infection control precautions for novel virulent Influenza viruses and sent to state or local health departments for testing. Viral culture should not be attempted in these cases unless a BSL 3+ facility is available to receive and culture specimens. | | Technological Principles | Multiplex nucleic acid | Same | | Analyte | DNA/RNA | Same | 16 {16} | Similarities | | | | --- | --- | --- | | Test Interpretation | Automated test interpretation and report generation. | Same | | Controls | Two controls are included in each reagent pouch to control for sample processing and both stages of PCR and melt analysis. | Same | | User Complexity | Moderate/Low | Same | | Time to result | Approximately 1 hour | Same | | Reagent Storage | Room temperature | Same | | Differences | | | | --- | --- | --- | | Item | New Device: FilmArray Pneumonia Panel plus (K181324) | Predicate: FilmArray Respiratory Panel 2 plus (DEN170017) | | Specimen Types | Sputum-like (induced or expectorated sputum, endotracheal aspirates) and BAL-like (BAL or mini-BAL) specimens | Nasopharyngeal swabs | | Result types | Detection with bin values (in 1-log rounded copies/mL bins) for Bacteria Qualitative for Atypical Bacteria, Antimicrobial Resistance Genes, and Viruses | Qualitative for all analytes | | Instrumentation | FilmArray, FilmArray 2.0, or FilmArray Torch | FilmArray 2.0 or FilmArray Torch | ### K. Standard/Guidance Document Referenced: - Guidance for Industry and Food and Drug Administration Staff – Highly Multiplexed Microbiological/Medical Countermeasure In Vitro Nucleic Acid Based Diagnostic Devices, (August 27, 2014) - Guidance for Industry and FDA Staff - Class II Special Controls Guidance Document: Respiratory Viral Panel Multiplex Nucleic Acid Assay (October 9, 2009) - Guidance for Industry and FDA Staff - Class II Special Controls Guidance Document: Testing for Detection and Differentiation of Influenza A Virus Subtypes Using Multiplex Nucleic Acid Assays (October 9, 2009) - Guidance for Industry and FDA Staff - Class II Special Controls Guidance Document: Testing for Human Metapneumovirus (hMPV) Using Nucleic Acid Assays (October 9, 2009) - Guidance for Industry and FDA Staff- Statistical Guidance on Reporting Results from Studies Evaluating Diagnostic Tests, (March 13, 2007) - Guidance for Sponsors, Institutional Review Boards, and Food and Drug Administrative Staff – Guidance on Informed Consent for In Vitro Diagnostic Device 17 {17} Studies Using Leftover Human Specimens that are Not Individually Identifiable, (April 25, 2006) - Evaluation of Stability of In Vitro Diagnostic Reagents; Approved Guideline, Clinical and Laboratory Standards Institute (CLSI) – First Edition, EP25-A (September 23, 2009). - Interference Testing in Clinical Chemistry; Approved Guideline, Clinical and Laboratory Standards Institute (CLSI) – Second Addition, EP07-A2 (November, 2005). - Molecular Diagnostic Methods for Infectious Diseases; Approved Guideline, Clinical and Laboratory Standards Institute (CLSI), MM3-A2 (February 2006) - User Protocol for Evaluation of Qualitative Test Performance; Approved Guideline, Clinical and Laboratory Standards Institute (CLSI)– Second Edition, EP12-A2 (January, 2008) - ISO 13485:2016/EN ISO 13485:2016, ‘Medical devices – Quality management systems – Requirements for regulatory purposes’. - ISO 14971:2007 ‘Medical devices – Application of risk management to medical devices’. - EN 13612:2002, ‘Performance evaluation of in vitro diagnostic devices’. - EN 13641:2002, ‘Elimination or reduction of risk of infection related to in vitro diagnostic reagents’. - EN 62366:2008/IEC 62366-1:2015, ‘Medical Devices-Application of usability engineering to medical devices’. - EN ISO 23640:2015, ‘In vitro diagnostic medical devices – Evaluation of stability of in vitro diagnostic reagents’. - Guidance for the Content of Premarket Submissions for Software Contained in Medical Devices, FDA Guidance Document (May 11, 2005) - Guidance for Industry, FDA Reviewers and Compliance on Off-The-Shelf Software Use in Medical Devices (September 9, 1999) - General Principle of Software Validation; Final Guidance for Industry and FDA Staff (January 11, 2002) - Content of Premarket Submissions for Management of Cybersecurity in Medical Devices (October 02, 2014) - Postmarket Management of Cybersecurity in Medical Devices (December 28, 2016) - ISO 62304:2006, ‘Medical device software – Software life-cycle processes’ – IEC 62304:2006, November 27, 2008. - Use of Symbols on Labels and in Labeling of In Vitro Diagnostic Devices Intended for Professional Use, FDA Guidance Document (November 30, 2004) - Guidance for Industry and FDA on Alternative to Certain Prescription Device Labeling Requirements (January 1, 2000) - ISO 15223-1:2016, ‘Medical Devices – Symbols to be used with medical device labels, labeling and information to be supplied – Part 1: General requirements’. - EN ISO 18113-1:2011, ‘In vitro diagnostic medical devices – Information supplied by the manufacturer (labeling) – Part 1: Terms, definition and general requirements’. - EN ISO 18113-2:2011, ‘In vitro diagnostic medical devices – Information supplied by the manufacturer (labeling) – Part 2: In vitro diagnostic reagents for professional use’. 18 {18} # L. Test Principle: The FilmArray Pneumonia Panel plus pouch is a closed system disposable that stores all the necessary reagents for sample preparation, reverse transcription, polymerase chain reaction (PCR), and detection in order to isolate, amplify, and detect nucleic acid from multiple lower respiratory pathogens within a single bronchoalveolar lavage (BAL)-like (BAL or mini-BAL) or sputum-like (sputum or ETA) specimen. After sample collection, the user injects hydration solution and sample combined with sample buffer into the pouch, places the pouch into a FilmArray instrument, and starts a run. The entire run process takes about one hour. Additional detail can be found in the appropriate FilmArray Operator's Manual. During a run, the FilmArray system: - Lyses the sample by agitation (bead beading). - Extracts and purifies all nucleic acids from the sample using magnetic bead technology. - Performs nested multiplex PCR by: o First performing reverse transcription and a single, large volume, massively-multiplexed reaction (PCR1) o Then performing multiple singleplex second-stage PCR reactions (PCR2) to amplify sequences within the PCR1 products - Uses endpoint melting curve data to detect and generate a result for each target on the FilmArray Pneumonia Panel plus array. - For the FilmArray Pneumonia Panel plus, the system also uses real-time amplification data from the assays relative to a Quantified Standard Material (QSM) included in the pouch to provide an estimated value in genomic copies per milliliter (copies/mL) for bacterial analytes. # M. Performance Characteristics (if/when applicable): # 1. Analytical performance: # a. Analytical Sensitivity: A limit of detection (LoD) was established for MERS-CoV as well as atypical bacteria and viruses detected by the FilmArray Pneumonia Panel plus. LoD was estimated by testing dilutions of contrived BAL or sputum samples containing known concentrations of organisms. Confirmation of LoD was achieved by testing at least 20 replicates per samples type on FilmArray, FilmArray 2.0 and FilmArray Torch systems (60 replicates total per sample type). LoD concentration was confirmed when the analyte was detected in at least 95% of the replicates tested. The confirmed LoD for each atypical bacterium or virus detected by the panel (including a LoD for more than one isolate of the more genetically diverse viruses) is listed in Table 5. The LoD concentration is based on quantification of each culture in viable units (TCID50/mL or CFU/mL) and a corresponding molecular LoD 19 {19} concentration (DNA or RNA copies/mL) is provided based on quantitative real-time or digital PCR. Table 5: Summary of Limit of Detection (LoD) for FilmArray Pneumonia Panel plus Atypical Bacteria and Viruses | Analyte | Isolate Strain/Serotype/ Source ID | LoD Concentration^{a} | | | --- | --- | --- | --- | | | | Viable Units | Molecular (DNA or RNA) | | Atypical Bacteria | | | | | *Chlamydia pneumoniae* | TW183 ATCC VR-2282 | 5.0E-01 TCID50/mL^{b} | 3.3E+02 copies/mL^{b} | | *Legionella pneumophila* | Philadelphia-1 ATCC 33152 | 5.0E+02 CFU/mL | 1.6E+03 copies/mL | | *Mycoplasma pneumoniae* | M129 Zeptometrix 0801579 | 7.5E+01 TCID50/mL^{b} | 3.5E+03 copies/mL^{b} | | Viruses | | | | | Middle East Respiratory Syndrome Coronavirus | EMC/2012 BEI NR-50171 (heat-inactivated) | 5.0E+01 TCID50/mL^{c} | 3.2E+03 copies/mL^{c} | | Adenovirus | Species A (A18) ATCC VR-19 | 5.0E+01 TCID50/mL | 9.2E+03 copies/mL | | | Species B (B3) Zeptometrix 0810062CF | 1.0E+00 TCID50/mL | 1.8E+03 copies/mL | | | Species C (C2) ATCC VR-846 | 5.0E+00 TCID50/mL | 7.5E+03 copies/mL | | | Species D (D37) Zeptometrix 0810119CF | 2.5E-01 TCID50/mL^{b} | 2.9E+03 copies/mL^{b} | | | Species E (E4) Zeptometrix 0810070CF | 1.0E-01 TCID50/mL^{b} | 3.5E+04 copies/mL^{b} | | | Species F (F41) ATCC VR-930 | 5.0E+00 TCID50/mL | 5.5E+03 copies/mL | | Coronavirus | 229E | 5.0E-01 TCID50/mL | 8.1E+01 copies/mL | | | HKU1 Clinical Specimen^{d} | - | 1.0E+04 copies/mL | | | NL63 BEI NR-470 | 2.5E+00 TCID50/mL^{c} | 5.4E+02 copies/mL^{c} | | | OC43 ATCC VR-759 | 5.0E+02 TCID50/mL^{c} | 9.3E+03 copies/mL^{c} | | Human Metapneumovirus | 16 Type A1 Zeptometrix 0810161CF | 5.0E+01 TCID50/mL | 5.9E+03 copies/mL | | Human Rhinovirus/ Enterovirus | Rhinovirus Type 1A Zeptometrix 810012CFN | 1.5E+01 TCID50/mL^{b} | 6.6E+03 copies/mL^{b} | | | Echovirus 6 Zeptometrix 0810076CF | 1.0E+02 TCID50/mL | 5.7E+02 copies/mL | 20 {20} | Analyte | Isolate Strain/Serotype/Source ID | LoD Concentration^{a} | | | --- | --- | --- | --- | | | | Viable Units | Molecular (DNA or RNA) | | Influenza A | H1N1pdm09 A/SwineNY/03/09 Zeptometrix 0810249CF | 2.5E+00 TCID50/mL^{c} | 1.7E+03 copies/mL^{c} | | | H3N2 A/Port Chalmers/1/73 ATCC VR-810 | 1.0E+00 TCID50/mL^{b} | 2.1E+02 copies/mL^{b} | | Influenza B | B/FL/04/06 Zeptometrix 0810255CF | 5.0E+00 TCID50/mL^{c} | 4.2E+02 copies/mL^{c} | | Parainfluenza Virus | Type 1 Zeptometrix 0810014CF | 2.5E+01 TCID50/mL | 5.2E+03 copies/mL | | | Type 2 Zeptometrix 0810015CF | 2.5E+01 TCID50/mL^{c} | 1.5E+03 copies/mL^{c} | | | Type 3 Zeptometrix 0810016CF | 2.5E+01 TCID50/mL^{c} | 3.8E+02 copies/mL^{c} | | | Type 4A Zeptometrix 0810060CF | 2.5E+02 TCID50/mL | 8.1E+03 copies/mL | | Respiratory Syncytial Virus | Type A Zeptometrix 0810040ACF | 1.0E+00 TCID50/mL | 4.3E+02 copies/mL | $^{a}$ The listed concentration was confirmed with ≥95% detection on each FilmArray system in artificial BAL (aBAL) and/or sputum. $^{b}$ LoD confirmation (≥95% detection) was achieved at a 2 to 5-fold lower concentration in aBAL. $^{c}$ LoD confirmation (≥95% detection) was achieved at a 2 to 5-fold lower concentration in sputum. $^{d}$ No cultured isolates of Coronavirus HKU1 were available for testing. For bacteria, the FilmArray Pneumonia Panel plus reports a Detected result when the estimated bacterial nucleic acid abundance is ≥10$^{3.5}$ copies/mL, and the panel reports a Not Detected if there is no amplification or the estimated bacterial nucleic acid abundance is <10$^{3.5}$ copies/mL. No assay-specific LoD concentrations were determined for the bacterial analytes, however, each assay was determined to be linear (slope ≈ 1.0 and coefficient of determination (Adj R2) >0.95) and estimates of nucleic acid abundance were determined to be accurate within 0.5 log$_{10}$ copies/mL when compared to an input concentration determined by digital PCR. Antimicrobial resistance (AMR) genes are reported as Detected when an applicable bacterium is detected and the assay for the AMR gene is positive. No AMR gene assay-specific LoD concentrations were determined for the AMR gene, but positive AMR gene assay results were recorded in ≥95% of 90 replicates of applicable bacteria tested at concentrations of 1.0E+04 copies/mL or less in the precision evaluation (see Precision below). ### b. Reproducibility: A multisite reproducibility study of the FilmArray Pneumonia Panel plus was performed with contrived BAL samples over multiples days at three laboratory locations (sites) on a combination of FilmArray, FilmArray 2.0 and FilmArray Torch 21 {21} systems. Testing incorporated a range of potential sources of variability, including run-to-run, day-to-day, and site-to-site variability, which also encompassed different operators, instruments, systems and reagent lots for a total of 30 tests per system and 90 total replicates per sample/concentration. Evaluation of the reproducibility of Detected/Not Detected results for atypical bacteria and viruses included samples containing combinations of five different analytes, at Negative, Low Positive (1×LoD), and Moderate Positive (3×LoD) concentrations. Negative results were obtained from up to 24 additional samples (see evaluation of precision for bacterial analytes below) that were not spiked with the analyte. A summary of results (percent (%) agreement with the expected Detected or Not Detected result) for each atypical bacterium and virus (by site and system) is provided Table 6 below. Table 6: Reproducibility of FilmArray Pneumonia Panel plus Atypical Bacteria and Virus Results | Analyte | Concentration Tested | Expected Result | Agreement with Expected Result | | | | | --- | --- | --- | --- | --- | --- | --- | | | | | FilmArray | FilmArray 2.0 | FilmArray Torch | All Sites [95% CI] | | | | | Site A | Site B | Site C | | | **Atypical Bacteria** | | | | | | | | *Chlamydia pneumoniae* | None (No Analyte) | Not Detected | 780/780 100% | 780/780 100% | 780/780 100% | 2,340/2,340 100% [99.8%-100%] | | *Legionella pneumophila* Philadelphia-1 ATCC 33152 | Moderate Positive 3×LoD 1.5E+03 CFU/mL | Detected | 30/30 100% | 30/30 100% | 30/30 100% | 90/90 100% [96%-100%] | | | Low Positive 1×LoD 5.0E+02 CFU/mL | Detected | 30/30 100% | 30/30 100% | 30/30 100% | 90/90 100% [96%-100%] | | | None (No Analyte) | Not Detected | 720/720 100% | 720/720 100% | 720/720 100% | 2,160/2,160 100% [99.8%-100%] | | *Mycoplasma pneumoniae* | None (No Analyte) | Not Detected | 780/780 100% | 780/780 100% | 780/780 100% | 2,340/2,340 100% [99.8%-100%] | | **Viruses** | | | | | | | 22 {22} | Analyte | Concentration Tested | Expected Result | Agreement with Expected Result | | | | | --- | --- | --- | --- | --- | --- | --- | | | | | FilmArray | FilmArray 2.0 | FilmArray Torch | All Sites [95% CI] | | | | | Site A | Site B | Site C | | | Middle East Respiratory Syndrome Coronavirus | None (No Analyte) | Not Detected | 780/780 100% | 780/780 100% | 780/780 100% | 2,340/2,340 100% [99.8%-100%] | | Adenovirus Species B Serotype 3 ZeptoMetrix 0810062CF | Moderate Positive 3×LoD 3.0E+00 TCID_{50}/mL | Detected | 30/30 100% | 30/30 100% | 30/30 100% | 90/90 100% [96%-100%] | | | Low Positive 1×LoD 1.0E+00 TCID_{50}/mL | Detected | 30/30 100% | 30/30 100% | 30/30 100% | 90/90 100% [96%-100%] | | | None (No Analyte) | Not Detected | 720/720 100% | 720/720 100% | 720/720 100% | 2,160/2,160 100% [99.8%-100%] | | Coronavirus | None (No Analyte) | Not Detected | 780/780 100% | 776/780 99.5% | 780/780 100% | 2,336/2,340 99.8% [99.6%-100%] | | Human Metapneumovirus 16 Type A1 ZeptoMetrix 0810161CF | Moderate Positive 3×LoD 1.5E+02 TCID_{50}/mL | Detected | 30/30 100% | 30/30 100% | 30/30 100% | 90/90 100% [96%-100%] | | | Low Positive 1×LoD 5.0E+01 TCID_{50}/mL | Detected | 30/30 100% | 29/30 96.7% | 30/30 100% | 89/90 98.9% [94%-100%] | | | None (No Analyte) | Not Detected | 720/720 100% | 720/720 100% | 720/720 100% | 2,160/2,160 100% [99.8%-100%] | | Human Rhinovirus/ Enterovirus | None (No Analyte) | Not Detected | 779/780 99.9% | 780/780 100% | 779/780 99.9% | 2,338/2,340 99.9% [99.7%-100%] | | Influenza A H3N2 A/Port Chalmers/1/73 ATCC VR-810 | Moderate Positive 3×LoD 1.5E+00 TCID_{50}/mL | Detected | 30/30 100% | 30/30 100% | 30/30 100% | 90/90 100% [96%-100%] | | | Low Positive 1×LoD 0.5E-01 TCID_{50}/mL | Detected | 30/30 100% | 29/30 96.7% | 30/30 100% | 89/90 98.9% [94%-100%] | | | None (No Analyte) | Not Detected | 720/720 100% | 720/720 100% | 720/720 100% | 2,160/2,160 100% [99.8%-100%] | 23 {23} | Analyte | Concentration Tested | Expected Result | Agreement with Expected Result | | | | | --- | --- | --- | --- | --- | --- | --- | | | | | FilmArray | FilmArray 2.0 | FilmArray Torch | All Sites [95% CI] | | | | | Site A | Site B | Site C | | | Influenza B | None (No Analyte) | Not Detected | 780/780 100% | 780/780 100% | 780/780 100% | 2,340/2,340 100% [99.8%-100%] | | Parainfluenza Virus Type 2 ZeptoMetrix 0810015CF | Moderate Positive 3×LoD 7.5E+01 TCID_{50}/mL | Detected | 30/30 100% | 30/30 100% | 30/30 100% | 90/90 100% [96%-100%] | | | Low Positive 1×LoD 2.5E+01 TCID_{50}/mL | Detected | 30/30 100% | 30/30 100% | 30/30 100% | 90/90 100% [96%-100%] | | | None (No Analyte) | Not Detected | 720/720 100% | 720/720 100% | 720/720 100% | 2,160/2,160 100% [99.8%-100%] | | Respiratory Syncytial Virus | None (No Analyte) | Not Detected | 780/780 100% | 780/780 100% | 780/780 100% | 2,340/2,340 100% [99.8%-100%] | Precision for bacterial analytes was measured at each concentration as 1) precision of bin results and 2) reproducibility of analyte detection. When a sample containing one or more bacteria is tested repeatedly, the precision of the bin results (probability that each replicate will receive the same bin result) will vary based on the concentration of nucleic acid measured and the relation of that concentration to the limits of each bin. Bin precision may be as low as 50% for values at a bin limit and precision will increase (up to 90% or higher) as the distance of the measured value from a bin limit increases. The precision of FilmArray Pneumonia Panel plus bin results will follow the model illustrated in Figure 1: - >90% at a bin center (Scenario 1) - ~60 – 90% between a bin limit and bin center (Scenario 2) - ~50% at bin limits (Scenario 3) 24 {24} ![img-0.jpeg](img-0.jpeg) Top: The probability (0.0 – 1.0) of the same bin results for each replicate tested varies based on proximity of the measured value to a bin limit. Bottom: Expected distribution of bin results at different mean measured values. Samples containing bacteria and corresponding antimicrobial (AMR) genes were tested at six different concentrations over the reportable range and below. A summary of the bin precision (percent (%) of replicates reported in each bin) and the reproducibility of detection is shown at each concentration tested in Table 7 below. Table 7: Reproducibility of FilmArray Pneumonia Panel plus Bacterial Bin Results on FilmArray, FilmArray 2.0 and FilmArray Torch* | Analyte | Concentration (log10 copies/mL) | % Replicates Reported in Each Bin Result | | | | | Total Detected | | --- | --- | --- | --- | --- | --- | --- | --- | | | | \( \geq 10^7 \) | \( 10^6 \) | \( 10^5 \) | \( 10^4 \) | ND | | | Acinetobacter baumannii (NDM-1) AR-BANK#0033 | 7.5 | 90/90(100%) | - | - | - | - | 90/90100% | | | 6.5 | 87/90(96.7%) | 3/90(3.3%) | - | - | - | 90/90100% | | | 5.5 | - | 82/90(91.1%) | 8/90(8.9%) | - | - | 90/90100% | | | 4.5 | - | 1/90(1.1%) | 80/90(88.9%) | 9/90 (10%) | - | 90/90100% | | | 3.5 | - | - | 1/90(1.1%) | 74/90(82.2%) | 15/90(16.7%) | 75/9083.3% | | | 2.5 | - | - | - | 1/90(1.1%) | 89/90(98.9%) | 1/901.1% | 25 {25} | Analyte | Concentration (log10 copies/mL) | % Replicates Reported in Each Bin Result | | | | | Total Detected | | --- | --- | --- | --- | --- | --- | --- | --- | | | | \( \geq 10^7 \) | \( 10^6 \) | \( 10^5 \) | \( 10^4 \) | ND | | | | None (No Analyte) | - | - | - | - | 1800/1800 (100%) | 0/1800 0% | | Enterobacter aerogenes ATCC 13048 | 7.5 | 90/90 (100%) | - | - | - | - | 90/90 100% | | | 6.5 | 65/90 (72.2%) | 25/90 (27.8%) | - | - | - | 90/90 100% | | | 5.5 | - | 52/90 (57.8%) | 38/90 (42.2%) | - | - | 90/90 100% | | | 4.5 | - | - | 38/90 (42.2%) | 51/90 (56.7%) | 1/90 (1.1%) | 89/90 98.9% | | | 3.5 | - | - | - | 33/90 (36.7%) | 57/90 (63.3%) | 33/90 36.7% | | | 2.5 | - | - | - | 1/90 (1.1%) | 89/90 (98.9%) | 1/90 1.1% | | | None (No Analyte) | - | - | - | - | 1800/1800 (100%) | 0/1800 0% | | Enterobacter cloacae (VIM) AR-BANK#0154 | 7.0 | 90/90 (100%) | - | - | - | - | 90/90 100% | | | 6.0 | 4/90 (4.4%) | 86/90 (95.6%) | - | - | - | 90/90 100% | | | 5.0 | - | 6/90 (6.7%) | 80/90 (88.9%) | - | 4/90 (4.4%) | 86/90 95.6% | | | 4.0 | - | - | 6/90 (6.7%) | 83/90 (92.2%) | 1/90 (1.1%) | 89/90 98.9% | | | 3.0 | - | - | 1/90 (1.1%) | 4/90 (4.4%) | 85/90 (94.4%) | 5/90 5.6% | | | 2.0 | - | - | - | - | 90/90 (100%) | 0/90 0% | | | None (No Analyte) | - | - | - | - | 1800/1800 (100%) | 0/1800 0% | | Escherichia coli (IMP) GRE 1062016 | 7.0 | 90/90 (100%) | - | - | - | - | 90/90 100% | | | 6.0 | 7/90 (7.8%) | 82/90 (91.1%) | - | - | 1/90 (1.1%) | 89/90 98.9% | | | 5.0 | - | 12/90 (13.3%) | 78/90 (86.7%) | - | - | 90/90 100% | | | 4.0 | - | - | 12/90 (13.3%) | 77/90 (85.6%) | 1/90 (1.1%) | 89/90 98.9% | | | 3.0 | - | - | 1/90 (1.1%) | 15/90 (16.7%) | 74/90 (82.2%) | 16/90 17.8% | | | 2.0 | - | - | - | - | 90/90 (100%) | 0/90 0% | | | None (No Analyte) | - | - | - | - | 1800/1800 (100%) | 0/1800 0% | | Haemophilus | 7.0 | 89/90 (98.9%) | 1/90 (1.1%) | - | - | - | 90/90 100% | 26 {26} | Analyte | Concentration (log10 copies/mL) | % Replicates Reported in Each Bin Result | | | | | Total Detected | | --- | --- | --- | --- | --- | --- | --- | --- | | | | \( \geq 10^7 \) | \( 10^6 \) | \( 10^5 \) | \( 10^4 \) | ND | | | influenzae ATCC 10211 | 6.0 | 35/90(48.9%) | 55/90(61.1%) | - | - | - | 90/90100% | | | 5.0 | - | 49/90(54.4%) | 40/90(44.4%) | 1/90(1.1%) | - | 90/90100% | | | 4.0 | - | - | 41/90(45.6%) | 49/90(54.4%) | - | 90/90100% | | | 3.0 | - | - | - | 42/90(46.7%) | 48/90(53.3%) | 42/9046.7% | | | 2.0 | - | - | - | - | 90/90(100%) | 0/900% | | | None (No Analyte) | - | - | - | - | 1800/1800(100%) | 0/18000% | | Klebsiella oxytoca (CTX-M) GRE 1254054 | 7.5 | 90/90(100%) | - | - | - | - | 90/90100% | | | 6.5 | 90/90(100%) | - | - | - | - | 90/90100% | | | 5.5 | 1/90(1.1%) | 84/90(93.3%) | 3/90(3.3%) | - | 2/90(2.2%) | 88/9097.8% | | | 4.5 | - | - | 89/90(98.9%) | - | 1/90(1.1%) | 89/9098.9% | | | 3.5 | - | - | - | 90/90(100%) | - | 90/90100% | | | 2.5 | - | - | 1/90(1.1%) | 1/90(1.1%) | 88/90(97.8%) | 2/902.2% | | | None (No Analyte) | - | - | - | - | 1800/1800(100%) | 0/18000% | | Klebsiella pneumoniae (KPC) AR-BANK#0097 | 7.00 | 90/90(100%) | - | - | - | - | 90/90100% | | | 6.00 | 12/90(13.3%) | 78/90(86.7%) | - | - | - | 90/90100% | | | 5.00 | - | 15/90(16.7%) | 75/90(83.3%) | - | - | 90/90100% | | | 4.00 | - | - | 23/90(25.6%) | 66/90(73.3%) | 1/90(1.1%) | 89/9098.9% | | | 3.00 | - | - | - | 15/90(16.7%) | 75/90(83.3%) | 15/9016.7% | | | 2.00 | - | - | - | - | 90/90(100%) | 0/900% | | | None (No Analyte) | - | - | - | - | 1800/1800(100%) | 0/18000% | | Moraxella catarrhalis ATCC 8176 | 7.0 | 90/90(100%) | - | - | - | - | 90/90100% | | | 6.0 | 26/90(28.9%) | 64/90(71.1%) | - | - | - | 90/90100% | | | 5.0 | - | 6/90(6.7%) | 83/90(92.2%) | 1/90(1.1%) | - | 90/90100% | 27 {27} | Analyte | Concentration (log10 copies/mL) | % Replicates Reported in Each Bin Result | | | | | Total Detected | | --- | --- | --- | --- | --- | --- | --- | --- | | | | \( \geq 10^7 \) | \( 10^6 \) | \( 10^5 \) | \( 10^4 \) | ND | | | | 4.0 | - | - | 4/90(4.4%) | 86/90(95.6%) | - | 90/90100% | | | 3.0 | - | - | - | 4/90(4.4%) | 86/90(95.6%) | 4/904.4% | | | 2.0 | - | - | - | - | 90/90(100%) | 0/900% | | | None(No Analyte) | - | - | - | - | 1800/1800(100%) | 0/18000% | | Proteus mirabilis ATCC 35659 | 7.0 | 88/90(97.8%) | - | - | - | 2/90(2.2%) | 88/9097.8% | | | 6.0 | 27/90(30%) | 63/90(70%) | - | - | - | 90/90100% | | | 5.0 | - | 26/90(28.9%) | 64/90(71.1%) | - | - | 90/90100% | | | 4.0 | - | - | 14/90(15.6%) | 75/90(83.3%) | 1/90(1.1%) | 89/9098.9% | | | 3.0 | - | - | - | 28/90(31.1%) | 62/90(68.9%) | 28/9031.1% | | | 2.0 | - | - | - | - | 90/90(100%) | 0/900% | | | None(No Analyte) | - | - | - | - | 1800/1800(100%) | 0/18000% | | Pseudomonas aeruginosa ATCC 10145 | 7.0 | 90/90(100%) | - | - | - | - | 90/90100% | | | 6.0 | 20/90(22.2%) | 70/90(77.8%) | - | - | - | 90/90100% | | | 5.0 | - | 24/90(26.7%) | 66/90(73.3%) | - | - | 90/90100% | | | 4.0 | - | - | 16/90(17.8%) | 74/90(82.2%) | - | 90/90100% | | | 3.0 | - | - | - | 14/90(15.6%) | 76/90(84.4%) | 14/9015.6% | | | 2.0 | - | - | - | - | 90/90(100%) | 0/900% | | | None(No Analyte) | - | - | - | - | 1800/1800(100%) | 0/18000% | | Serratia marcescens (OXA-48-like) GRE 1659005 | 7.0 | 90/90(100%) | - | - | - | - | 90/90100% | | | 6.0 | 2/90(2.2%) | 88/90(97.8%) | - | - | - | 90/90100% | | | 5.0 | - | 7/90(7.8%) | 83/90(92.2%) | - | - | 90/90100% | | | 4.0 | - | - | 6/90(6.7%) | 83/90(92.2%) | 1/90(1.1%) | 89/9098.9% | | | 3.0 | - | - | - | 6/90(6.7%) | 84/90(93.3%) | 6/906.7% | 28 {28} | Analyte | Concentration (log10 copies/mL) | % Replicates Reported in Each Bin Result | | | | | Total Detected | | --- | --- | --- | --- | --- | --- | --- | --- | | | | \( \geq 10^7 \) | \( 10^6 \) | \( 10^5 \) | \( 10^4 \) | ND | | | | 2.0 | - | - | - | - | 90/90(100%) | 0/900% | | | None(No Analyte) | - | - | - | - | 1800/1800(100%) | 0/18000% | | Staphylococcus aureus subsp. aureus (mecA/C and MREJ) ATCC 43300 | 7.0 | 90/90(100%) | - | - | - | - | 90/90100% | | | 6.0 | - | 90/90(100%) | - | - | - | 90/90100% | | | 5.0 | - | - | 90/90(100%) | - | - | 90/90100% | | | 4.0 | - | - | - | 89/90(98.9%) | 1/90(1.1%) | 89/9098.9% | | | 3.0 | - | - | - | - | 90/90(100%) | 0/900% | | | 2.0 | - | - | - | - | 90/90(100%) | 0/900% | | | None(No Analyte) | - | - | - | 2/1260(0.2%) | 1258/1260(99.8%) | 2/12600.2% | | Streptococcus agalactiae ATCC 13813 | 7.8 | 89/90(98.9%) | 1/90 (1.1%) | - | - | - | 90/90100% | | | 6.8 | 89/90(98.9%) | - | - | - | 1/90 (1.1%) | 89/9098.9% | | | 5.8 | - | 88/90(97.8%) | 1/90(1.1%) | 1/90(1.1%) | - | 90/90100% | | | 4.8 | - | - | 89/90(98.9%) | 1/90(1.1%) | - | 90/90100% | | | 3.8 | - | - | - | 86/90(95.6%) | 4/90(4.4%) | 86/9095.6% | | | 2.8 | - | - | - | 3/90(3.3%) | 87/90(96.7%) | 3/903.3% | | | None(No Analyte) | - | - | - | - | 1800/1800(100%) | 0/18000% | | Streptococcus pneumoniae ATCC 6303 | 6.5 | 90/90(100%) | - | - | - | - | 90/90100% | | | 5.5 | - | 90/90(100%) | - | - | - | 90/90100% | | | 4.5 | - | - | 89/90(98.9%) | 1/90(1.1%) | - | 90/90100% | | | 3.5 | - | - | - | 89/90(98.9%) | 1/90(1.1%) | 89/9098.9% | | | 2.5 | - | - | - | - | 90/90(100%) | 0/900% | | | 1.5 | - | - | - | - | 90/90(100%) | 0/900% | | | None(No Analyte) | - | - | - | - | 1800/1800(100%) | 0/18000% | 29 {29} | Analyte | Concentration (log10 copies/mL) | % Replicates Reported in Each Bin Result | | | | | Total Detected | | --- | --- | --- | --- | --- | --- | --- | --- | | | | ≥10^{7} | 10^{6} | 10^{5} | 10^{4} | ND | | | *Streptococcus pyogenes* ATCC 49399 | 7.8 | 90/90 (100%) | - | - | - | - | 90/90 100% | | | 6.8 | 90/90 (100%) | - | - | - | - | 90/90 100% | | | 5.8 | 5/90 (5.6%) | 84/90 (93.3%) | 1/90 (1.1%) | - | - | 90/90 100% | | | 4.8 | - | 3/90 (3.3%) | 87/90 (96.7%) | - | - | 90/90 100% | | | 3.8 | - | - | 3/90 (3.3%) | 87/90 (96.7%) | - | 90/90 100% | | | 2.8 | - | - | - | 16/90 (18.9%) | 74/90 (81.1%) | 16/90 17.8% | | | None (No Analyte) | - | - | - | - | 1800/1800 (100%) | 0/1800 0% | * Grey shading indicates the expected bin results based on the analyte concentration and bold font indicates the bin with the greatest percentage of results at each concentration. The precision of the antimicrobial resistance (AMR) genes was measured as the reproducibility of analyte detection on each system and overall. Results are presented in Table 8 as the percent of replicates that are detected at concentrations of the associated bacterium that are within the reportable range, or below the reportable range, as well as the percent agreement with the expected Not Detected result in unspiked samples. 30 {30} **Table 8: Reproducibility of FilmArray Pneumonia Panel *plus* Antimicrobial Resistance Gene Results on FilmArray, FilmArray 2.0 and FilmArray Torch** | AMR Gene Organism | Concentration of Organism (copies/mL log10) | Expected Result | Agreement with the Expected Result | | | | | --- | --- | --- | --- | --- | --- | --- | | | | | FilmArray | FilmArray 2.0 | FilmArray Torch | All Systems/Sites [95% CI] | | | | | Site A | Site B | Site C | | | **CTX-M** *Klebsiella oxytoca* **GRE 1254054** | **Reportable Range** | **Detected** | **150/150** 100% | **149/150** 99.3 | **150/150** 100% | **449/450** **99.8%** [98.8%-99.9%] | | | Below Reportable Range | Detected (Variable) | 0/30 0% | 1/30 3.3% | 0/30 0% | 1/90 1.1% [0.03%-6%] | | | None (No Analyte) | N/A or Not Detected | 600/600 100% | 599/600 99.8% | 600/600 100% | 1799/1800 99.9% [99.7%-100%] | | **IMP** *Escherichia coli* **GRE 1062016** | **Reportable Range** | **Detected** | **120/120** 100% | **120/120** 100% | **120/120** 100% | **360/360** **100%** [99%-100%] | | | Below Reportable Range | Detected (Variable) | 10/60 16.7% | 9/60 15% | 3/60 5% | 22/180 12.2% [7.8%-17.9%] | | | None (No Analyte) | N/A or Not Detected | 600/600 100% | 600/600 100% | 600/600 100% | 1800/1800 100% [99.8%-100%] | | **KPC** *Klebsiella pneumoniae* **AR-Bank#0097** | **Reportable Range** | **Detected** | **120/120** 100% | **119/120** 99.2% | **120/120** 100% | **359/360** **99.7%** [98.5%-100%] | | | Below Reportable Range | Detected (Variable) | 14/60 23.3% | 10/60 16.7% | 9/60 15% | 33/180 18.3% [13%-24.8%] | | | None (No Analyte) | N/A or Not Detected | 600/600 100% | 600/600 100% | 600/600 100% | 1800/1800 100% [99.8%-100%] | | **mecA/C and MREJ** *Staphylococcus aureus* **ATCC 43300** | **Reportable Range** | **Detected** | **119/120** 99.2% | **118/120** 98.3% | **120/120** 100% | **357/360** **99.2%** [97.6%-99.8%] | | | Below Reportable Range | Detected (Variable) | 0/60 0% | 0/60 0% | 0/60 0% | 0/180 0% [0%-2%] | | | None (No Analyte) | N/A or Not Detected | 420/420 100% | 420/420 100% | 420/420 100% | 1260/1260 100% [99.7%-100%] | | **NDM** *Acinetobacter baumannii* **AR-Bank#0033** | **Reportable Range** | **Detected** | **150/150** 100% | **149/150** 99.3% | **150/150** 100% | **449/450** **99.8%** [98.8%-100%] | | | Below Reportable Range | Detected (Variable) | 1/30 3.3% | 1/30 3.3% | 0/30 0% | 2/90 2.2% [0.3%-7.8%] | 31 {31} | AMR Gene Organism | Concentration of Organism (copies/mL log10) | Expected Result | Agreement with the Expected Result | | | | | --- | --- | --- | --- | --- | --- | --- | | | | | FilmArray | FilmArray 2.0 | FilmArray Torch | All Systems/Sites [95% CI] | | | | | Site A | Site B | Site C | | | | None (No Analyte) | N/A or Not Detected | 599/600 99.8% | 600/600 100% | 600/600 100% | 1799/1800 99.9% [99.7%-100%] | | OXA-48-like *Serratia marcescens* GRE 1659005 | Reportable Range | Detected | 120/120 100% | 119/120 99.2% | 120/120 100% | 359/360 99.70% [98.5%-100%] | | | Below Reportable Range | Detected (Variable) | 14/60 23.3% | 12/60 20% | 9/60 15% | 35/180 19.4% [13.9%-26%] | | | None (No Analyte) | N/A or Not Detected | 598/600 99.7% | 600/600 100% | 600/600 100% | 1798/1800 99.9% [99.6%-100%] | | VIM *Enterobacter cloacae* AR-BANK#0154 | Reportable Range | Detected | 120/120 100% | 120/120 100% | 120/120 100% | 360/360 100% [99%-100%] | | | Below Reportable Range | Detected (Variable) | 10/60 16.7% | 9/60 15% | 3/60 5% | 22/180 12.2% [7.8%-17.9%] | | | None (No Analyte) | N/A or Not Detected | 599/600 99.8% | 600/600 100% | 600/600 100% | 1799/1800 99.9% [99.7%-100%] | c. Linearity/assay reportable range: Linearity Linearity of the FilmArray Pneumonia Panel plus was performed to evaluate unbinned value response to changes in concentration and to determine if an offset exists between the unbinned value and a dPCR (digital PCR) determined molecular concentration (the unbinned value is calculated using real-time amplification data for the analyte relative to a known standard (Quantified Standard Material or QSM)). A series of contrived samples were prepared in artificial bronchoalveolar lavage (aBAL) matrix such that each bacterial analyte was tested at six different concentrations spanning 1.5 – 7.8 log10 (copies/mL). The input concentration of each cultured bacterium was determined by digital PCR (dPCR), which served as the reference concentrations for offset determination. Once prepared, each sample was tested repeatedly at each concentration on a single day for a total of eighteen replicate measures per analyte. The unbinned values generated by the FilmArray Pneumonia Panel plus assays were plotted as a function of the nominal (dPCR) input concentrations to determine the linearity of the response. All plot data were observed to be linear and this was confirmed through mathematical modeling. For each analyte, data bounding the 32 {32} reporting range (~3.0 – 7.0 log10 (copies/mL)) were fit using linear and quadratic models. In all cases, the linear fit model was preferred as it was sufficient to describe the change in unbinned values as a function of changing inputs and the addition of curvature did not improve the fit predictions. The best fit linear model coefficients for each bacterial FilmArray Pneumonia Panel plus assay were evaluated (slope, y-intercept, and coefficient of determination (Adj R²)). The slope provides a direct measure of how the unbinned value responds to changes in input concentration, where a slope near 1.0 demonstrates that the unbinned values change in direct proportion to the input concentration. The best fit slopes of the assays varied within the range of 0.975 – 1.114, demonstrating that changes in the unbinned values display a ~1:1 relationship to changes in the input concentration. The y-intercept from the linear equation represents the theoretical offset predicted to exist at a zero input concentration. The Adj R² value provides a measure of the goodness of fit between the linear model and the data, where values of 1.0 indicate perfect agreement and values of 0 indicate random association displaying no correlation. The best fit Adj R² values of the assays were high, ranging from 0.951 – 0.989, further demonstrating strong agreement between the data and the linear model. The FilmArray Pneumonia Panel plus unbinned value was shown to respond proportionately to changes in input concentration following a linear relationship defined by slopes around 1.0. The offset of each assay was found to be within the range 0.01 – 0.27-log10 (copies/mL) and does not change substantially as a function of concentration over the reportable range. These data demonstrate that the Pneumonia Panel unbinned value is accurate and thus that the FilmArray Pneumonia Panel plus reported bin results will accurately reflect the concentration of analytes in a test sample. d. Traceability, Stability, Expected values (controls, calibrators, or methods): ### Process Controls Two process controls are included in each pouch: RNA Process Control: The RNA Process Control assay targets an RNA transcript from the yeast Schizosaccharomyces pombe. The yeast is present in the pouch in a freeze-dried form and becomes rehydrated when sample is loaded. The control material is carried through all stages of the test process, including lysis, nucleic acid purification, reverse transcription, PCR1, dilution, PCR2, and DNA melting. A positive RNA Process Control result indicates that all steps carried out in the FilmArray Pneumonia Panel plus pouch were successful. Quantified Standard Material (QSM) Control: The QSM assay detects a quantified standard synth…
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