← Product Code [QDS](/submissions/PA/subpart-d%E2%80%94serological-reagents/QDS) · K181324

# FilmArray Pneumonia Panel plus (K181324)

_Biofire Diagnostics, LLC · QDS · Nov 15, 2018 · Pathology · SESE_

**Canonical URL:** https://fda.innolitics.com/submissions/MI/subpart-d%E2%80%94serological-reagents/QDS/K181324

## Device Facts

- **Applicant:** Biofire Diagnostics, LLC
- **Product Code:** [QDS](/submissions/PA/subpart-d%E2%80%94serological-reagents/QDS.md)
- **Decision Date:** Nov 15, 2018
- **Decision:** SESE
- **Submission Type:** Traditional
- **Regulation:** 21 CFR 866.4001
- **Device Class:** Class 2
- **Review Panel:** Pathology

## 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

Multi-center prospective study (8 U.S. sites, 2016-2017) evaluated 846 BAL and 836 sputum specimens. Comparator: quantitative reference culture (qRefCx) for bacteria, PCR/sequencing for others. Sensitivity/PPA and Specificity/NPA calculated. MERS-CoV performance supplemented by archived specimens. Contrived specimens (N=1225) used for rare analytes. Performance goals generally met; limitations noted for specific strains.

## 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).

## Regulatory 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

- FilmArray Respiratory Panel 2 plus (RP2plus) ([DEN170017](/device/DEN170017.md))

## Submission Summary (Full Text)

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## November 15, 2018

BioFire Diagnostics, LLC Kristen Kanack Senior Vice President, Regulatory & Clinical Affairs 515 Colorow Drive Salt Lake City, Utah 84108

Re: K181324

Trade/Device Name: FilmArray Pneumonia Panel plus Regulation Number: 21 CFR 866.4001 Regulation Name: MERS-CoV and common respiratory pathogens multiplex nucleic acid detection system Regulatory Class: Class II Product Code: ODS Dated: May 17, 2018 Received: May 18, 2018

Dear Kristen Kanack:

We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food. Drug, and Cosmetic Act (Act) that do not require approval of a premarket approval application (PMA). You may, therefore, market the device, subject to the general controls provisions of the Act. Although this letter refers to your product as a device, please be aware that some cleared products may instead be combination products. The 510(k) Premarket Notification Database located at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/pmn.cfm identifies combination product submissions. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.

If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. In addition, FDA may publish further announcements concerning your device in the Federal Register.

Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Part 

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801 and Part 809); medical device reporting of medical device-related adverse events) (21 CFR 803) for devices or postmarketing safety reporting (21 CFR 4, Subpart B) for combination products (see https://www.fda.gov/CombinationProducts/GuidanceRegulatoryInformation/ucm597488.html; good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820) for devices or current good manufacturing practices (21 CFR 4. Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm.

For comprehensive regulatory information about mediation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/) and CDRH Learn (http://www.fda.gov/Training/CDRHLearn). Additionally, you may contact the Division of Industry and Consumer Education (DICE) to ask a question about a specific regulatory topic. See the DICE website (http://www.fda.gov/DICE) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).

Sincerely.

## Steven R. Gitterman -S for

Uwe Scherf, Ph.D. Director Division of Microbiology Devices Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health

Enclosure

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# Indications for Use

510(k) Number (if known) K181342

Device Name FilmArray Pneumonia Panel plus

### Indications for Use (Describe)

The FilmArray® Pneumonia Panel plus is a multiplexed nucleic acid test intended for use with 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:

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

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

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

Atypical Bacteria

- Chlamydia pneumoniae
- · Legionella pneumophila
- Mycoplasma pneumoniae

Viruses

- · Adenovirus

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- · Coronavirus
- Human Metapneumovirus
- · Human Rhinovirus/Enterovirus
- · Influenza A
- · Influenza B
- · Parainfluenza Virus
- · Respiratory Syncytial Virus

Antimicrobial Resistance Genes

- · CTX-M
- IMP
- КРС
- 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.

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) 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 CFUmL. For specimens with multiple bacteria detected, the relative abundance of nucleic acids (copies/mL) may not correlate with the relative abundance of bacteria as determined by culture (CFU/mL). Clinical correlation is advised to determine significance of semi-quantitative Bin (copies/mL) for clinical management.

The antimicrobial resistance gene detected may or may not be associated with the agent(s) responsible for disease.

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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 deterial 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 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.

| Type of Use (Select one or both, as applicable)                                                                          |                                                                                                                         |
|--------------------------------------------------------------------------------------------------------------------------|-------------------------------------------------------------------------------------------------------------------------|
| <div> <span> <span style="font-size: 10pt;">☑</span> Prescription Use (Part 21 CFR 801 Subpart D)         </span> </div> | <div> <span> <span style="font-size: 10pt;">☐</span> Over-The-Counter Use (21 CFR 801 Subpart C)         </span> </div> |

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## 510(k) Summary BioFire Diagnostics, LLC

## FilmArray Pneumonia Panel plus

## Introduction:

According to the requirements of 21 CFR 807.92, the following information provides sufficient detail to understand the basis for a determination of substantial equivalence.

## Submitted by:

BioFire Diagnostics, LLC 515 Colorow Drive Salt Lake City, UT 84108

Telephone: 801-736-6354 Facsimile: 801-588-0507

Contact: Kristen J. Kanack, ext. 1330

Date Submitted: May 17, 2018

## Device Name and Classification:

Trade Name: FilmArray Pneumonia Panel plus

Regulation Number: 21 CFR 866.4001

Classification Name: MERS-CoV and common respiratory pathogens multiplex nucleic acid detection system

## Predicate Device:

DEN170017 - FilmArray Respiratory Panel 2 plus (RP2plus)

## Intended 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 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 

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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 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<br>complex                    | Klebsiella oxytoca             | Serratia marcescens      |
| Enterobacter cloacae complex                                        | Klebsiella pneumoniae<br>group | Staphylococcus aureus    |
| Escherichia coli                                                    | Moraxella catarrhalis          | Streptococcus agalactiae |
| Haemophilus influenzae                                              | Proteus spp.                   | Streptococcus pneumoniae |
| Klebsiella aerogenes                                                | Pseudomonas aeruginosa         | Streptococcus pyogenes   |

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

| Atypical Bacteria                            |                              |                             |
|----------------------------------------------|------------------------------|-----------------------------|
| Chlamydia pneumoniae                         | Legionella pneumophila       | Mycoplasma pneumoniae       |
| Viruses                                      |                              |                             |
| 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 BioFire Diagnostics 510(k) FilmArray Pneumonia Panel plus

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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 value. Detection of analytes does not rule out coinfection with other organisms; the agent(s) 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 semiquantitative 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 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.

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## Device Description:

The FilmArray Pneumonia Panel plus is designed to simultaneously identify Middle East Respiratory Syndrome Coronavirus (MERS-CoV) and 26 other potential pathogens of lower respiratory tract infection (LRTI) and seven 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) that allows the test results to be used in determining appropriate patient treatment and management.

The FilmArray Pneumonia Panel plus is compatible with BioFire's 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 pouch module) is used to perform FilmArray Pneumonia Panel testing on these systems.

| MERS-CoV – Qualitative Results                |                                                    |
|-----------------------------------------------|----------------------------------------------------|
| Middle East Respiratory Syndrome Coronavirus  |                                                    |
| Other Common Lower Respiratory Pathogens      |                                                    |
| Bacteria -Results with Bin Values             | Antimicrobial Resistance Genes                     |
| Acinetobacter calcoaceticus-baumannii complex | blaCTX-M (Extended spectrum beta-lactamase (ESBL)) |
| Enterobacter cloacae complex                  | blaIMP (Carbapenem resistance)                     |
| Escherichia coli                              | blaKPC (Carbapenem resistance)                     |
| Haemophilus influenzae                        | mecA/mecC and MREJ (Methicillin resistance)        |
| Klebsiella aerogenes                          | 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                        |                                                    |

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

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The FilmArray instruments contain coordinated systems of inflatable bladders and seal points, which act on the pouch to control the movement of liquid between the pouch blisters. When a bladder is inflated over a reagent blister, it forces liquid from the blister into connecting channels. Alternatively, when a seal is placed over a connecting channel it acts as a valve to open or close a channel. In addition, electronicallycontrolled 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 conclusion of the 2nd stage PCR, the array is interrogated by melt curve analysis for the detection of signature amplicons denoting the presence of specific targets. A digital camera placed in front of the 2nd stage PCR captures fluorescent images of the PCR reactions and software interprets the data.

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

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

## Substantial Equivalence:

The FilmArray Pneumonia Panel plus is substantially equivalent to the FilmArray Respiratory Panel 2 plus (RP2plus) Application (DEN170017), which was cleared on November 24, 2017 and determined to be a Class II device under the classification product code QDS.

Table 1 compares the FilmArray Pneumonia Panel plus to the FilmArray Respiratory Panel 2 plus (RP2plus) and outlines the similarities and differences between the two systems.

| Element            | New Device:<br>FilmArray Pneumonia Panel plus                                                                       | Predicate:<br>FilmArray Respiratory Panel 2 plus (RP2plus)<br>(DEN170017) |
|--------------------|---------------------------------------------------------------------------------------------------------------------|---------------------------------------------------------------------------|
| Specimen Types     | Sputum-like (induced or expectorated sputum,<br>endotracheal aspirates) and BAL-like (BAL or<br>mini-BAL) specimens | NPS in viral transport medium                                             |
| Organisms Detected | Middle East Respiratory Syndrome Coronavirus<br>(MERS-CoV)                                                          | Middle East Respiratory Syndrome Coronavirus<br>(MERS-CoV)                |

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| Element                                                                                                                                      | New Device:<br>FilmArray Pneumonia Panel plus                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    | Predicate:<br>FilmArray Respiratory Panel 2 plus (RP2plus)<br>(DEN170017)                                                                                                                                                                                                                                                                                                                                                                                                                        |
|----------------------------------------------------------------------------------------------------------------------------------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
|                                                                                                                                              | Bacteria: Acinetobacter calcoaceticus-baumannii<br>complex, Enterobacter cloacae complex,<br>Escherichia coli , Haemophilus influenzae,<br>Klebsiella oxytoca, Klebsiella aerogenes,<br>Klebsiella pneumoniae group, Moraxella<br>catarrhalis, Proteus spp., Pseudomonas<br>aeruginosa, Serratia marcescens, Staphylococcus<br>aureus, Streptococcus agalactiae, Streptococcus<br>pneumoniae, Streptococcus pyogenes<br>Atypical Bacteria: Chlamydia pneumoniae,<br>Legionella pneumophila, Mycoplasma<br>pneumoniae<br>Antimicrobial Resistance Genes: CTX-M, IMP,<br>KPC, mecA/C + MREJ, NDM, Oxa48-like, VIM<br>Viruses: Adenovirus, Coronavirus, Human<br>Metapneumovirus, Human<br>Rhinovirus/Enterovirus, Influenza A, Influenza B,<br>Parainfluenza virus,<br>Respiratory Syncytial virus | Bacteria: Bordetella parapertussis (IS 1001),<br>Bordetella pertussis (ptxP), Chlamydia<br>pneumoniae, Mycoplasma pneumoniae<br>Viruses: Adenovirus, Coronavirus 229E,<br>Coronavirus HKU1, Coronavirus NL63,<br>Coronavirus OC43, Human Metapneumovirus,<br>Human Rhinovirus/Enterovirus, Influenza A,<br>including subtypes H1, H1-2009, and H3,<br>Influenza B, Parainfluenza Virus 1, Parainfluenza<br>Virus 2, Parainfluenza Virus 3, Parainfluenza<br>Virus 4, Respiratory Syncytial Virus |
| Analyte                                                                                                                                      | DNA/RNA                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          | Same                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             |
| Technological<br>Principles                                                                                                                  | Multiplex nucleic acid                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           | Same                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             |
| Result types                                                                                                                                 | Detection with bin values (in 1-log rounded<br>copies/mL bins) for Bacteria<br>Qualitative for MERS-CoV, Atypical Bacteria,<br>Antimicrobial Resistance Genes, and Viruses                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       | Qualitative for all analytes                                                                                                                                                                                                                                                                                                                                                                                                                                                                     |
| Instrumentation                                                                                                                              | FilmArray, FilmArray 2.0, or FilmArray Torch                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     | FilmArray 2.0 or FilmArray Torch                                                                                                                                                                                                                                                                                                                                                                                                                                                                 |
| Time to result                                                                                                                               | About 1 hour                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     | ~ 45 minutes                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     |
| Reagent Storage                                                                                                                              | Room temperature                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 | Same                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             |
| Test Interpretation                                                                                                                          | Automated test interpretation and report<br>generation. User cannot access raw data.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             | Same                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             |
| Controls<br>Two controls are included in each reagent pouch<br>to control for sample processing and both stages<br>of PCR and melt analysis. |                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  | Same                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             |
| User Complexity                                                                                                                              | Moderate/Low                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     | Same                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             |

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## Summary of Performance Data

## Clinical Performance

The clinical performance of the FilmArray Pneumonia Panel plus was established during a multi-center study conducted at eight geographically distinct U.S. study sites from October 2016 to July 2017. A total of 904 residual BAL (including mini-BAL) and 925 residual sputum (821 BAL and 83 mini-BAL) and 925 residual sputum (478 sputum and 447 ETA) specimens were acquired for the prospective clinical study. FilmArray Pneumonia Panel plus performance in BAL and mini-BAL was similar, as was performance in sputum and ETA; therefore these sample types are not stratified further in performance tables. A total of 58 BAL and 89 sputum specimens were excluded from the final data analysis. The most common reasons for specimen exclusion for both specimen types was reference culture unable to be performed, the specimen was found to not meet the inclusion criteria after the specimen had been enrolled, or the study site was unable to complete the Case Report Form (CRF). The final data set consisted of 846 BAL and 836 sputum specimens. Table 3 provides a summary of demographic information for the specimens included in the prospective study.

| BAL          |               |           |              |          |              |          |          |              |          |          |  |       |     |     |    |     |    |     |     |
|--------------|---------------|-----------|--------------|----------|--------------|----------|----------|--------------|----------|----------|--|-------|-----|-----|----|-----|----|-----|-----|
|              |               | Overall   | Site 1ª      | Site 2   | Site 3       | Site 4   | Site 5   | Site 6       | Site 7   | Site 8   |  |       |     |     |    |     |    |     |     |
| Sex          | Male          | 480 (57%) | 80 (59%)     | 7 (54%)  | 138<br>(55%) | 21 (68%) | 75 (61%) | 82 (52%)     | 27 (61%) | 50 (55%) |  |       |     |     |    |     |    |     |     |
|              | Female        | 366 (43%) | 55 (41%)     | 6 (46%)  | 113<br>(45%) | 10 (32%) | 48 (39%) | 76 (48%)     | 17 (39%) | 41 (45%) |  |       |     |     |    |     |    |     |     |
| Age          | ≤ 5 years     | 23 (3%)   | 0 (0%)       | 5 (38%)  | 0 (0%)       | 15 (48%) | 0 (0%)   | 3 (2%)       | 0 (0%)   | 0 (0%)   |  |       |     |     |    |     |    |     |     |
|              | 6 - 17 years  | 27 (3%)   | 0 (0%)       | 8 (62%)  | 0 (0%)       | 13 (42%) | 0 (0%)   | 4 (3%)       | 1 (2%)   | 1 (1%)   |  |       |     |     |    |     |    |     |     |
|              | 18 - 34 years | 70 (8%)   | 18 (13%)     | 0 (0%)   | 17 (7%)      | 3 (10%)  | 10 (8%)  | 10 (6%)      | 5 (11%)  | 7 (8%)   |  |       |     |     |    |     |    |     |     |
|              | 35 - 65 years | 470 (56%) | 78 (58%)     | 0 (0%)   | 152<br>(61%) | 0 (0%)   | 70 (57%) | 88 (56%)     | 27 (61%) | 55 (60%) |  |       |     |     |    |     |    |     |     |
|              | > 65 years    | 255 (30%) | 38 (28%)     | 0 (0%)   | 82 (33%)     | 0 (0%)   | 43 (35%) | 53 (34%)     | 11 (25%) | 28 (31%) |  |       |     |     |    |     |    |     |     |
| Care Setting | Hospitalized  | 666 (79%) | 116<br>(86%) | 12 (92%) | 223<br>(89%) | 9 (29%)  | 82 (67%) | 118<br>(75%) | 25 (57%) | 81 (89%) |  |       |     |     |    |     |    |     |     |
|              | Outpatient    | 159 (19%) | 18 (13%)     | 0 (0%)   | 28 (11%)     | 22 (71%) | 31 (25%) | 39 (25%)     | 14 (32%) | 7 (8%)   |  |       |     |     |    |     |    |     |     |
|              | Emergency     | 21 (2%)   | 1 (1%)       | 1 (8%)   | 0 (0%)       | 0 (0%)   | 10 (8%)  | 1 (1%)       | 5 (11%)  | 3 (3%)   |  | Total | 846 | 135 | 13 | 251 | 31 | 123 | 158 |
| Emergency    | 21 (2%)       | 1 (1%)    | 1 (8%)       | 0 (0%)   | 0 (0%)       | 10 (8%)  | 1 (1%)   | 5 (11%)      | 3 (3%)   |          |  |       |     |     |    |     |    |     |     |
|              | Total         | 846       | 135          | 13       | 251          | 31       | 123      | 158          | 44       | 91       |  |       |     |     |    |     |    |     |     |

Table 2. Overall and Per Site Demographic Analysis for BAL Specimens

ª Subject age could not be determined for one specimen from Site 1

## Table 3. Overall and Per Site Demographic Analysis for Sputum Specimens

|                | Sputum        |              |              |          |              |              |          |          |          |              |
|----------------|---------------|--------------|--------------|----------|--------------|--------------|----------|----------|----------|--------------|
|                | Overall       | Site 1       | Site 2       | Site 3   | Site 4       | Site 5       | Site 6   | Site 7   | Site 8   |              |
| Sex            | Male          | 481<br>(58%) | 66 (59%)     | 54 (54%) | 136<br>(56%) | 97 (61%)     | 14 (82%) | 31 (53%) | 34 (74%) | 49 (47%)     |
|                | Female        | 355<br>(42%) | 45 (41%)     | 46 (46%) | 105<br>(44%) | 61 (39%)     | 3 (18%)  | 28 (47%) | 12 (26%) | 55 (53%)     |
| Age            | ≤ 5 years     | 138<br>(17%) | 0 (0%)       | 49 (49%) | 0 (0%)       | 80 (51%)     | 0 (0%)   | 0 (0%)   | 2 (4%)   | 7 (7%)       |
|                | 6 - 17 years  | 107<br>(13%) | 0 (0%)       | 35 (35%) | 0 (0%)       | 64 (41%)     | 0 (0%)   | 0 (0%)   | 2 (4%)   | 6 (6%)       |
|                | 18 - 34 years | 86 (10%)     | 15 (14%)     | 16 (16%) | 20 (8%)      | 13 (8%)      | 1 (6%)   | 6 (10%)  | 5 (11%)  | 10 (10%)     |
|                | 35 - 65 years | 284<br>(34%) | 51 (46%)     | 0 (0%)   | 133<br>(55%) | 1 (1%)       | 6 (35%)  | 36 (61%) | 20 (43%) | 37 (36%)     |
|                | > 65 years    | 221<br>(26%) | 45 (41%)     | 0 (0%)   | 88 (37%)     | 0 (0%)       | 10 (59%) | 17 (29%) | 17 (37%) | 44 (42%)     |
| Care<br>Settil | Hospitalized  | 682<br>(82%) | 106<br>(95%) | 64 (64%) | 219<br>(91%) | 105<br>(66%) | 12 (71%) | 52 (88%) | 23 (50%) | 101<br>(97%) |

BioFire Diagnostics 510(k) FilmArray Pneumonia Panel plus

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| Sputum     |          |        |          |         |          |         |        |          |        |
|------------|----------|--------|----------|---------|----------|---------|--------|----------|--------|
|            | Overall  | Site 1 | Site 2   | Site 3  | Site 4   | Site 5  | Site 6 | Site 7   | Site 8 |
| Outpatient | 73 (9%)  | 2 (2%) | 14 (14%) | 18 (7%) | 24 (15%) | 2 (12%) | 5 (8%) | 7 (15%)  | 1 (1%) |
| Emergency  | 81 (10%) | 3 (3%) | 22 (22%) | 4 (2%)  | 29 (18%) | 3 (18%) | 2 (3%) | 16 (35%) | 2 (2%) |
| Total      | 836      | 111    | 100      | 241     | 158      | 17      | 59     | 46       | 104    |

All specimens were evaluated with the FilmArray Pneumonia Panel plus at clinical study sites. Refrigerated specimen aliquots were sent to a central reference laboratory for quantitative reference culture (qRefCx) and frozen specimen aliquots were also sent to BioFire for evaluation by polymerase chain reaction (PCR)/sequencing-based comparator methods.

The reference methods used in this study were as follows:

Bacterial analytes were compared to qRefCx to evaluate sensitivity and specificity, and the method was considered positive for the presence of the organism of interest if it was recovered in culture and enumerated at a level of 3162 (10^3.5) CFU/mL or greater.

Bacterial analytes were also evaluated by comparison to a single PCR assay for the organism of interest followed by a quantitative molecular assay that included sequencing (qMol) to assess FilmArray bin reporting performance. Atypical bacteria and viruses were compared to two conventional PCR assays followed by bidirectional sequencing. For specimens with an applicable bacteria detected by FilmArray, AMR genes were compared to a single PCR assay (from the specimen) followed by sequencing. A specimen was considered to be positive for an analyte if bi-directional sequencing data meeting predefined quality acceptance criteria matched organism-specific sequences deposited in the NCBI GenBank database (www.ncbi.nlm.nih.gov) with acceptable E-values. When two PCR comparator assays were used, any specimen that tested negative by both of the comparator assays was considered Negative.

No reference testing was performed for MERS-CoV as this virus was not circulating in the United States at the time of enrollment; therefore all specimens were assumed to be negative.

Positive Percent Agreement (PPA) or Sensitivity for each analyte was calculated as 100% x (TP / (TP + FN)). True positive (TP) indicates that both the FilmArray Pneumonia Panel plus and the comparator method had a positive result for this specific analyte, and false negative (FN) indicates that the FilmArray Pneumonia Panel plus result was negative while the comparator result was positive. Negative Percent Agreement (NPA) or Specificity was calculated as 100% x (TN + FP)). True negative (TN) indicates that both the FilmArray Pneumonia Panel plus and the comparator method had negative results, and a false positive (FP) indicates that the FilmArray Pneumonia Panel plus result was positive but the comparator result was negative. The exact binomial two-sided 95% confidence interval was calculated. Samples for which false positive and/or false negative results (i.e., discrepant results) were obtained when comparing the FilmArray Pneumonia Panel plus results to the comparator method results were further investigated. The discrepancy investigations were primarily performed as follows: for discrepancies between the Pneumonia Panel plus and reference culture for bacterial analytes, discrepancies were first examined to see if qRefCx or FilmArray had observed the analyte but reported it as "negative" or "Not Detected" because it was below the detection threshold. If this did not resolve the discrepancy, the results of qMol testing were considered. And if these methods still did not resolve the discrepancy, it was then investigated in the same manner as other analytes that used molecular comparator (i.e. using multiple additional molecular assays followed by sequence analysis). The results of SOC testing were also

{13}------------------------------------------------

considered. The prospective clinical study results are summarized in Table 5 for BAL and sputum specimens, respectively.

| BAL                                                        |           |                 |                 |            |                 |      |            |  |  |  |
|------------------------------------------------------------|-----------|-----------------|-----------------|------------|-----------------|------|------------|--|--|--|
|                                                            | Reference |                 | Sensitivity/PPA |            | Specificity/NPA |      |            |  |  |  |
| Analyte                                                    | Method    | TP/(TP +<br>FN) | %               | 95%CI      | TN/(TN +<br>FP) | %    | 95%CI      |  |  |  |
| Middle East Respiratory Syndrome Coronavirus<br>(MERS-CoV) | PCR/Seq   | 0/0             | -               |            | 846/846         | 100  | 99.5-100%  |  |  |  |
| Bacteria                                                   |           |                 |                 |            |                 |      |            |  |  |  |
| Acinetobacter calcoaceticus-baumannii complexb             | qRefCx    | 0/0             | -               |            | 839/846         | 99.2 | 98.3-99.6% |  |  |  |
| Enterobacter cloacae complexc                              | qRefCx    | 11/12           | 91.7            | 64.6-98.5% | 822/834         | 98.6 | 97.5-99.2% |  |  |  |
| Escherichia colid                                          | qRefCx    | 12/12           | 100             | 75.8-100%  | 826/834         | 99.0 | 98.1-99.5% |  |  |  |
| Haemophilus influenzaee                                    | qRefCx    | 10/10           | 100             | 72.2-100%  | 764/836         | 91.4 | 89.3-93.1% |  |  |  |
| Klebsiella aerogenesf                                      | qRefCx    | 6/7             | 85.7            | 48.7-97.4% | 832/839         | 99.2 | 98.3-99.6% |  |  |  |
| Klebsiella oxytocag                                        | qRefCx    | 2/2             | 100             | 34.2-100%  | 835/844         | 98.9 | 98.0-99.4% |  |  |  |
| Klebsiella pneumoniae grouph                               | qRefCx    | 15/15           | 100             | 79.6-100%  | 819/831         | 98.6 | 97.5-99.2% |  |  |  |
| Moraxella catarrhalisi                                     | qRefCx    | 0/0             | -               |            | 817/846         | 96.6 | 95.1-97.6% |  |  |  |
| Proteus spp.j                                              | qRefCx    | 5/5             | 100             | 56.6-100%  | 837/841         | 99.5 | 98.8-99.8% |  |  |  |
| Pseudomonas aeruginosak                                    | qRefCx    | 36/36           | 100             | 90.4-100%  | 772/810         | 95.3 | 93.6-96.6% |  |  |  |
| Serratia marcescensl                                       | qRefCx    | 6/6             | 100             | 61.0-100%  | 834/840         | 99.3 | 98.5-99.7% |  |  |  |
| Staphylococcus aureusm                                     | qRefCx    | 46/47           | 97.9            | 88.9-99.6% | 729/799         | 91.2 | 89.1-93.0% |  |  |  |
| Streptococcus agalactiaen                                  | qRefCx    | 1/1             | 100             |            | 821/845         | 97.2 | 95.8-98.1% |  |  |  |
| Streptococcus pneumoniaeo                                  | qRefCx    | 5/5             | 100             | 56.6-100%  | 817/841         | 97.1 | 95.8-98.1% |  |  |  |
| Streptococcus pyogenesp                                    | qRefCx    | 2/2             | 100             | 34.2-100%  | 838/844         | 99.3 | 98.5-99.7% |  |  |  |
| Atypical Bacteria                                          |           |                 |                 |            |                 |      |            |  |  |  |
| Chlamydia pneumoniaeq                                      | PCR/Seq   | 0/0             | -               |            | 844/845         | 99.9 | 99.3-100%  |  |  |  |
| Legionella pneumophilar                                    | PCR/Seq   | 2/2             | 100             | 34.2-100%  | 833/833         | 100  | 99.5-100%  |  |  |  |
| Mycoplasma pneumoniaes                                     | PCR/Seq   | 3/3             | 100             | 43.9-100%  | 841/842         | 99.9 | 99.3-100%  |  |  |  |
| Viruses                                                    |           |                 |                 |            |                 |      |            |  |  |  |
| Adenovirus                                                 | PCR/Seq   | 8/8             | 100             | 67.6-100%  | 837/837         | 100  | 99.5-100%  |  |  |  |
| Coronavirust                                               | PCR/Seq   | 18/21           | 85.7            | 65.4-95.0% | 810/823         | 98.4 | 97.3-99.1% |  |  |  |
| Human Metapneumovirusu                                     | PCR/Seq   | 8/8             | 100             | 67.6-100%  | 836/837         | 99.9 | 99.3-100%  |  |  |  |
| Human Rhinovirus/Enterovirusv                              | PCR/Seq   | 52/54           | 96.3            | 87.5-99.0% | 771/782         | 98.6 | 97.5-99.2% |  |  |  |
| Influenza Aw                                               | PCR/Seq   | 10/10           | 100             | 72.2-100%  | 830/833         | 99.6 | 98.9-99.9% |  |  |  |
| Influenza Bx                                               | PCR/Seq   | 5/6             | 83.3            | 43.6-97.0% | 837/838         | 99.9 | 99.3-100%  |  |  |  |
| Parainfluenza Virusy                                       | PCR/Seq   | 16/18           | 88.9            | 67.2-96.9% | 824/826         | 99.8 | 99.1-99.9% |  |  |  |
| Respiratory Syncytial Virus                                | PCR/Seq   | 3/3             | 100             | 43.9-100%  | 841/841         | 100  | 99.5-100%  |  |  |  |

Table 4. FilmArray Pneumonia Panel plus Clinical Performance Summary for BAL Specimens®

® The performance measures of sensitivity and specificity only refer to the bacterial analytes for which the gold-stand of qReferice method. Performance measures of PPA and NPA refer to all other analytes, for which PCR/sequencing assays were used as comparator methods.

* Evidence of ACB complex was found in all seven FP specimens; one was enumerated below 10°3.5 CFUmL by qRefCx and six were detected by QMol.

& E. cloace complex was observed in the 10% bin by the FilmArray Preumonia Panel plus. Evidence of E. cloacae complex was found in all 12 FP specimens; six were enumerated below 10'3.5 CFU/mL by qRefCx, five were detected using an additional molecular method.

^ Evidence of E. coli was found in all eight FP speciment six were enumerated below 10°3.5 CFU/mL by qRefCx and two were detected by qMol.

* Evidence of H. influenzae was found in all 72 FP specimented below 10°3.5 CFUmL by qRefCx, 56 were detected by aMol, eight were detected using an additional molecular method, and one was identified in SOC culture.

f K. aerogenes was identified in the single FN speciment in all seven FP specimens was found in all seven FP specimens; four were enumerated below 10^3.5 CFU/mL by qRefCx and three were detected by qMol.

9 Evidence of K. oxytoca was found in all nine FP speciments three were enumerated below 1043.5 CFU/mL by qRefCx, five were detected by qMol, and one was detected using an additional molecular method.

{14}------------------------------------------------

" Evidence of K. pneumoniae group was found in all 12 FP speciment seven were enumerated below 10'3.5 CFU/mL by gRefCx, four were detected by qMol, and one was detected using an additional molecular method.

'Evidence of M. catarthalis was found in all 29 FP speciments two were enumerated below 10°3.5 CFUmL by qRefCx, 25 were detected by qMol, and two were detected using an additional molecular method.

'Evidence of Proteus spp. was found in all four FP speciments three were enumerated below 103.5 CFUmL by qRefCx and one was detected by QMol.

* Evidence of P. aeruginosa was found in all 38 FP specimented below 10°3.5 CFUmL by qRefCx, 16 were detected by gMol, and three were detected using an additional molecular method

'Evidence of S. marcescens was found in all six FP specimens; four were enumerated below 10°3.5 CFUmL by qRefCx and two were detected by QMol.

™ S. aureus was detected in the single FN specifical molecular method. Evidence of S. aureus was found in 6970 FP specimens; 29 were enumerated below 10%.5 CFUmL by qRefCx, 30 were detected using an additional molecular method, and two were identified in SOC culture.

" Evidence of S. agalactiae was found in all 24 FP speciments seven were enumerated below 10°3.5 CFU/mL by qRefCv, 13 were detected by qMol, and four were detected using an additional molecular method.

° Evidence of S. pneumoniae was found in all 24 FP specimerated below 10°3.5 CFUmL by qReCx, 18 were detected by gMol, and one was detected using an additional molecular method.

P Evidence of S. pyogenes was found in all six FP speciments two were enumerated below 10°3.5 CFU/mL by qRefCx, three were was detected using an additional molecular method.

9 The single FP specimen was negative for C. pneumoniae when tested with additional methods during discrepancy investigation.

' The single FP specimen was negative for M. pneumoniae when tested with additional methods during discrepancy investigation.

\$ CoV was detected in 2/3 FN and 8/13 FP specimens using an additional molecular method.

™ The single FP specimen was negative for hMPV when tested with additional methods during discrepancy investigation.

" HRV/EV was detected in both FN specimens using and HRV/EV was detected in 8/1 FP specimens during discrepancy investigation; seven were detected using an additional method and one was detected upon FilmArray Pneumonia Panel plus retest.

Y FluA was detected in 2/3 FP specimens using an additional molecular method.

" FluB was detected in the single FilmArray Pneumonia Panel plus retest. FluB was detected in the single FP specimen using an additional molecular method.

* PIV was detected in both FN and both FP specimens using an additional molecular method.

#### Table 5. FilmArray Pneumonia Panel plus Clinical Performance Summary for Sputum Specimens®

| Sputum                                                     |           |                 |      |            |                 |      |            |
|------------------------------------------------------------|-----------|-----------------|------|------------|-----------------|------|------------|
|                                                            | Reference | Sensitivity/PPA |      |            | Specificity/NPA |      |            |
| Analyte                                                    | Method    | TP/(TP +<br>FN) | %    | 95%CI      | TN/(TN +<br>FP) | %    | 95%CI      |
| Middle East Respiratory Syndrome Coronavirus<br>(MERS-CoV) | PCR/Seq   | 0/0             | -    | -          | 836/836         | 100  | 99.5-100%  |
|                                                            |           | Bacteria        |      |            |                 |      |            |
| Acinetobacter calcoaceticus-baumannii complexb             | qRefCx    | 10/11           | 90.9 | 62.3-98.4% | 807/825         | 97.8 | 96.6-98.6% |
| Enterobacter cloacae complexc                              | qRefCx    | 11/12           | 91.7 | 64.6-98.5% | 803/824         | 97.5 | 96.1-98.3% |
| Escherichia colid                                          | qRefCx    | 23/24           | 95.8 | 79.8-99.3% | 787/812         | 96.9 | 95.5-97.9% |
| Haemophilus influenzaee                                    | qRefCx    | 16/18           | 88.9 | 67.2-96.9% | 727/818         | 88.9 | 86.5-90.9% |
| Klebsiella aerogenesf                                      | qRefCx    | 3/4             | 75.0 | 30.1-95.4% | 823/832         | 98.9 | 98.0-99.4% |
| Klebsiella oxytocag                                        | qRefCx    | 9/9             | 100  | 70.1-100%  | 817/827         | 98.8 | 97.8-99.3% |
| Klebsiella pneumoniae grouph                               | qRefCx    | 21/23           | 91.3 | 73.2-97.6% | 769/813         | 94.6 | 92.8-95.9% |
| Moraxella catarrhalisi                                     | qRefCx    | 5/5             | 100  | 56.6-100%  | 761/831         | 91.6 | 89.5-93.3% |
| Proteus spp.j                                              | qRefCx    | 15/15           | 100  | 79.6-100%  | 813/821         | 99.0 | 98.1-99.5% |
| Pseudomonas aeruginosak                                    | qRefCx    | 103/106         | 97.2 | 92.0-99.0% | 673/730         | 92.2 | 90.0-93.9% |
| Serratia marcescensl                                       | qRefCx    | 26/27           | 96.3 | 81.7-99.3% | 782/809         | 96.7 | 95.2-97.7% |
| Staphylococcus aureusm                                     | qRefCx    | 111/112         | 99.1 | 95.1-99.8% | 631/724         | 87.2 | 84.5-89.4% |
| Streptococcus agalactiaen                                  | qRefCx    | 9/9             | 100  | 70.1-100%  | 793/827         | 95.9 | 94.3-97.0% |
| Streptococcus pneumoniaeo                                  | qRefCx    | 16/16           | 100  | 80.6-100%  | 785/820         | 95.7 | 94.1-96.9% |
| Streptococcus pyogenesp                                    | qRefCx    | 6/6             | 100  | 61.0-100%  | 825/830         | 99.4 | 98.6-99.7% |
| Atypical Bacteria                                          |           |                 |      |            |                 |      |            |
| Chlamydia pneumoniae                                       | PCR/Seq   | 0/0             | -    | -          | 835/835         | 100  | 99.5-100%  |
| Legionella pneumophilaq                                    | PCR/Seq   | 0/1             | 0    | -          | 826/826         | 100  | 99.5-100%  |
| Mycoplasma pneumoniaer                                     | PCR/Seq   | 7/8             | 87.5 | 52.9-97.8% | 827/827         | 100  | 99.5-100%  |
| Viruses                                                    |           |                 |      |            |                 |      |            |

{15}------------------------------------------------

| Sputum                        |                  |              |      |            |              |      |            |
|-------------------------------|------------------|--------------|------|------------|--------------|------|------------|
| Analyte                       | Reference Method | TP/(TP + FN) | %    | 95%CI      | TN/(TN + FP) | %    | 95%CI      |
| Adenoviruss                   | PCR/Seq          | 13/17        | 76.5 | 52.7-90.4% | 815/817      | 99.8 | 99.1-99.9% |
| Coronavirust                  | PCR/Seq          | 28/32        | 87.5 | 71.9-95.0% | 796/802      | 99.3 | 98.4-99.7% |
| Human Metapneumovirusu        | PCR/Seq          | 20/21        | 95.2 | 77.3-99.2% | 812/813      | 99.9 | 99.3-100%  |
| Human Rhinovirus/Enterovirusv | PCR/Seq          | 96/96        | 100  | 96.2-100%  | 717/730      | 98.2 | 97.0-99.0% |
| Influenza Aw                  | PCR/Seq          | 13/13        | 100  | 77.2-100%  | 819/822      | 99.6 | 98.9-99.9% |
| Influenza Bx                  | PCR/Seq          | 12/12        | 100  | 75.8-100%  | 821/823      | 99.8 | 99.1-99.9% |
| Parainfluenza Virusy          | PCR/Seq          | 28/29        | 96.6 | 82.8-99.4% | 804/806      | 99.8 | 99.1-99.9% |
| Respiratory Syncytial Virusz  | PCR/Seq          | 43/43        | 100  | 91.8-100%  | 787/791      | 99.5 | 98.7-99.8% |

® The performance measures of sensitivity only refer to the bacterial analyes for which the gold-standard of qRefCx was used as the reference method. Performance measures of PPA and NPA refer to all other analytes, for which PCR/sequencing as comparator methods

· The isolate recovered from the single the molentified by oReCx; molecular testing of the isolate identified it as Pseudomonas fluorescens during discrepancy investigation. Evidence of ACB complex 15 were detected by gMol, two were detected using an additional molecular method, and one was identified in SOC culture.

· E. cloace complex was detected in the single FN specific an additional molecular method. Evidence of E. cloace complex was found in all 21 FP specimens; four were enumerated below 10°3.5 CFUmL by qReCx; 16 were detected using an additional molecular method.

d E. coli was observed in the single FN speciment of the FilmArray Pneumonia Panel plus. Evidence of E. coll was found in all 25 FP specimens; six were enumerated below 10°3.5 CFUlmL by qRefCx, 14 were detected using an additional molecular method

* H. influenzae was delected in 1/2 FN speciment from the other FN specimen was misidentified by qReCx; molecular testing of the isolate identified it as Haemophilus haemolyticus during discription. Evidence of H. influenzae was found in all 91 F P specimens; four were enumerated below 10°3.5 CFUmL by qReCx, 78 were detected by gMol, seven were detected using an additional method, and two were identified in SOC culture.

TThe isolate recovered from the single intiled by qReCx; molecular testing of the isolate identified it as Hafria paralvei during discrepancy investigation. Evidence of K. aerogenes was found in all nine FP specimens; three were enumerated below 10°3.5 CFUmL by qRol, and one was detected using an additional molecular method.

® Evidence of K. oxytoca was found in all 10 FP speciments three were enumerated below 10°3.5 CFUmL by qRefCx, five were detected using an additional molecular method.

* K. pneumoniae group was detected in 1/2 FN speciment to be a result of a specimen swap at the central reference laboratory. Evidence of K. pneumoriae group was found in 43/44 FP specimens; 15 were enumerated below 10°3.5 CFU/mL by qRefCx, 21 were detected by gMol, and seven were detected using an additional molecular method.

'Evidence of M. catarrhalis was found in all 70 FP speciments one was enumerated below 10°3.5 CFU/mL by gReCx, 63 were detected using an additional molecular method, and one was identified in SOC culture.

 Evidence of Proteus sp. was found in all eight FP specimented below 10°3.5 CFUmL by gRefOx, four were delected by gMol, and wo were detected using an additional molecular method.

r P. aerginosa was observed in 1/3 FN speciment be 104 bin by the FilmAray Pneumonia Panel plus. The isolates recovered from the other two FN specimens were misidentified by qRefCx; nolecular testing one as Pseudomonas denitrificans and the other as Pseudomonas flurescens during discrepancy investigation. Evidence of P. aeruginosa was found in all 57 FP speciments; 21 were enumerated below 1093.5 CFUmL by gRefCx, 33 were detected by gMol. two were detected using an additional molecular method, and one was identified in SOC culture.

1 S. marcescens was observed in the single FN speciment of 104 bin by the Filmlerray Preumonia Panel plus. Evidence of S. marcessers was found in 2027 FP specimens; seven were enumerated below 10°3.5 CFU/mL by gReCx, 16 were detected using an additional molecular meltod.

™ S. aureus was observed in the single FN speciment the 10% bin by the FilmArray Pneumonia Panel plus. Evidence of S. aureus was found in all 93 FP specimens; 43 were enumerated below 10°3.5 CFUlmL by qReCx; 43 were detected using an additional molecular method, and four were identified in SOC culture.

" Evidence of S. agalactiae was found in all 34 FP speciments in below 10°3.5 CFUmL by qRefCx, 24 were detected by qMol, and five were detected using an additional molecular method

º Evidence of S. pneumoniae was found in all 35 FP speciments one was enumerated below 10°3.5 CFU/mL by qRefCx and 34 were detected by QMol.

P Evidence of S. pyogenes was found in all five FP speciments of the mas detected using an additional molecular method.

a L. pneumophila was detected in the single FN specimen using an additional molecular method.

' The single FN specimen was negative for M. pneumoniae when tested with an additional method during discrepancy investigation.

\$ AdV was detected in all four FN and 1/2 FP specimens using an additional molecular method.

↑ CoV was detected in all four FN and 3/6 FP specimens using an additional molecular method.

" MPV was delected in the single FN specimen using an method. The single FP specimen was negative for MPV when tested with an additional molecular method during discrepancy investigation.

" HRV/EV was detected in 12/13 FP specimens during in were detected using an additional molecular method and one was delected upon FilmArray Pneumonia Panel plus retest.

* FluA was detected in all three FP specimens using an additional molecular method.

* Both FP specimens were negative for FluB when tested with additional methods during discrepancy investigation.

Y PIV was detected in the single FN and 1/2 FP specimens using an additional molecular method.

² RSV was detected in all four FP specimens using an additional molecular method.

BioFire Diagnostics 510(k) FilmArray Pneumonia Panel plus 

{16}------------------------------------------------

A total of 156 BAL specimens and 295 sputum specimens received a FilmArray Pneumonia Panel plus Detected result for at least one applicable gram-negative bacterium on the panel and reported results for CTX-M, IMP, KPC, NDM, OXA-48-like, and VIM; a total of 94 BAL specimens and 196 sputum specimens received a FilmArray Pneumonia Panel plus Detected result for at least one appli…

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**Source:** [https://fda.innolitics.com/submissions/MI/subpart-d%E2%80%94serological-reagents/QDS/K181324](https://fda.innolitics.com/submissions/MI/subpart-d%E2%80%94serological-reagents/QDS/K181324)

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