The FilmArray® Pneumonia Panel is a multiplexed nucleic acid test intended for use with FilmArray® 2.0 or FilmArray® Torch systems for the simultaneous detection of multiple respiratory viral and bacterial nucleic acids, as well as select antimicrobial resistance genes, in sputum-like specimens (induced or expectorated sputum, or endotracheal aspirates) or bronchoalveolar lavage (BAL)-like specimens (BAL or mini-BAL) obtained from individuals suspected of lower respiratory tract infection.

The following bacteria are reported semi-quantitatively with bins representing approximately 10^4, 10^5 genomic copies of bacterial nucleic acid per milliliter (copies/mL) of specimen, to aid in estimating relative abundance of nucleic acid from these common bacteria within a specimen:

Bacteria reported with bins of 10^4, 10^5, 10^6, or ≥10^7 copies/mL
-Acinetobacter calcoaceticus-baumannii complex

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

The following atypical bacteria, viruses, and antimicrobial resistance genes are reported qualitatively: Atypical Bacteria -Chlamydia pneumoniae -Legionella pneumophila

-Mycoplasma pneumoniae
Viruses -Adenovirus
-Coronavirus
-Human Metapneumovirus
-Human Rhinovirus/Enterovirus
-Influenza A
-Influenza B
-Parainfluenza Virus
-Respiratory Syncytial Virus

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

The detection and identification of specific viral and bacterial nucleic acids, as well as the estimation of relative abundance of nucleic acid from common bacterial analytes, within specimens collected from individuals exhibiting signs and/or symptoms of a respiratory infection, aids in the diagnosis of lower respiratory infection with other clinical and epidemiological information. The results of this test should not be used as for diagnosis, treatment, or other patient management decisions.

Negative results in the setting of a respiratory illness may be due to infection with pathogens that are not detected by this test, pathogens below the limit of detection, or in the case of bacterial analytes, present at levels below the lowest reported 10^4 copies/mL bin. Detection of analytes does not rule out co-infection with other organisms; the agent(s) detected by the FilmArray Pneumonia Panel may not be the definite cause of disease. Additional laboratory testing (e.g. bacterial and viral culture, immunofluorescence, and radiography) may be necessary when evaluating a patient with possible lower respiratory tract infection.

Detection of bacterial nucleic acid may be indicative of colonizing or normal respiratory flora and may not indicate the causative agent of pneumonia. Semi-quantitative Bin (copies/mL) results generated by the FilmArray Pneumonia Panel are not equivalent to CFU/mL and do not consistently correlate with the quantity of bacterial analytes compared to CFUmL. For specimens with multiple bacteria detected, the relative abundance of nucleic acids (copies/mL) may not correlate with the relative abundance of bacteria as determined by culture (CFU/mL). Clinical correlation is advised to determine significance of semi-quantitative Bin (copies/mL) for clinical management.

The antimicrobial resistance gene detected may or may not be associated with the agent(s) responsible for disease. Negative results for these antimicrobial resistance gene assays do not indicate susceptibility to corresponding classes of antimicrobials, as multiple mechanisms of antimicrobial resistance exist.

Antimicrobial resistance can occur via multiple mechanisms. A "Not Detected" result for a genetic marker of antimicrobial resistance does not indicate susceptibility to associated antimicrobial drugs or drug classes. A "Detected" result for a genetic marker of antimicrobial resistance cannot be definitively linked to the microorganism(s) detected. Culture is required to obtain isolates for antimicrobial susceptibility testing, and FilmArray Pneumonia Panel results should be used in conjunction with culture results for determination of bacterial susceptibility or resistance.

Due to the genetic similarity between human rhinovirus and enterovirus, the test cannot reliably differentiate them. A positive Rhinovirus Enterovirus result should be followed up using an alternate method (e.g., cell culture or sequence analysis) if differentiation is required.

Culture is required to identify pathogens not detected by the FilmArray Pneumonia Panel, to further speciate analytes in genus, complex, or group results if desired, to identify bacterial pathogens present below the 10^4 copies/mL bin if desired, and for antimicrobial susceptibility testing.

Device Description

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

Bacteria - Quantitative Results: Acinetobacter calcoaceticus-baumannii complex, Enterobacter cloacae complex, Escherichia coli, Haemophilus influenzae, Klebsiella aerogenes, Klebsiella oxytoca, Klebsiella pneumoniae group, Moraxella catarrhalis, Proteus spp., Pseudomonas aeruginosa, Serratia marcescens, Staphylococcus aureus, Streptococcus agalactiae, Streptococcus pneumoniae, Streptococcus pyogenes
Bacteria (Atypical) - Qualitative Results: Chlamydia pneumoniae, Legionella pneumophila, Mycoplasma pneumoniae
Antimicrobial Resistance Genes: blaCTX-M (Extended spectrum beta-lactamase (ESBL)), blaIMP (Carbapenem resistance), blaKPC (Carbapenem resistance), mecA/mecC and MREJ (Methicillin resistance), blaNDM (Carbapenem resistance), blaOXA48-like (Carbapenem resistance), blaVIM (Carbapenem resistance)
Viruses: Adenovirus, Coronavirus, Human Metapneumovirus, Human Rhinovirus/Enterovirus, Influenza A, Influenza B, Parainfluenza Virus, Respiratory Syncytial Virus

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

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

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

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

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

AI/ML Overview

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

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

1. Table of Acceptance Criteria and Reported Device Performance

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

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

Analyte (Specific Focus)	Acceptance Criteria (Original expectation)	Reported Device Performance (Under specific conditions)
Adenovirus C (when pouch is within 6 months of expiration)	Consistent sensitivity	LoD for adenovirus species C is 10 – 100 x impaired (loss in sensitivity) when pouches are within 6 months of expiration. Increased risk of false negative Adenovirus results.
All other analytes / Adenovirus C (when pouch is > 6 months from expiration)	Consistent sensitivity	Performance is not impacted.

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

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

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

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

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

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

4. Adjudication Method

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

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

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

6. Standalone (Algorithm Only) Performance

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

7. Type of Ground Truth Used

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

8. Sample Size for the Training Set

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

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

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

Summary

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September 22, 2021

Image /page/0/Picture/1 description: The image contains the logo of the U.S. Food and Drug Administration (FDA). On the left is the Department of Health & Human Services logo. To the right of that is the FDA logo, which is a blue square with the letters "FDA" in white. To the right of the blue square is the text "U.S. FOOD & DRUG ADMINISTRATION" in blue.

BioFire Diagnostics, LLC Kevin Bourzac Vice President, Regulatory & Clinical Affairs 515 Colorow Drive Salt Lake City, Utah 84108

Re: K212727

Trade/Device Name: FilmArray Pneumonia Panel Regulation Number: 21 CFR 866.3985 Regulation Name: Device To Detect And Identify Microorganisms And Associated Resistance Marker Nucleic Acids Directly In Respiratory Specimens Regulatory Class: Class II Product Code: QDP Dated: August 26, 2021 Received: August 27, 2021

Dear Kevin Bourzac:

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

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requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Part 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/combination-products/guidance-regulatory-information/postmarketing-safety-reportingcombination-products); good manufacturing practice requirements as set forth in the quality systems (OS) 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 https://www.fda.gov/medical-device-safety/medical-device-reportingmdr-how-report-medical-device-problems.

For comprehensive regulatory information about mediation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/medicaldevices/device-advice-comprehensive-regulatory-assistance) and CDRH Learn (https://www.fda.gov/training-and-continuing-education/cdrh-learn). 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 (https://www.fda.gov/medical-device-advice-comprehensive-regulatoryassistance/contact-us-division-industry-and-consumer-education-dice) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).

Sincerely,

Maria I. Garcia -S

Maria Ines Garcia, Ph.D. Branch Chief Division of Microbiology Devices OHT7: Office of In Vitro Diagnostics and Radiological Health Office of Product Evaluation and Quality Center for Devices and Radiological Health

Enclosure

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Indications for Use

510(k) Number (if known) K180966

Device Name FilmArray Pneumonia (PN) Panel

Indications for Use (Describe)

The following bacteria are reported semi-quantitatively with bins representing approximately 10°4, 10°5 genomic copies of bacterial nucleic acid per milliliter (copies/mL) of specimen, to aid in estimating relative abundance of nucleic acid from these common bacteria within a specimen:

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

-Acinetobacter calcoaceticus-baumannii complex

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

The following atypical bacteria, viruses, and antimicrobial resistance genes are reported qualitatively: Atypical Bacteria -Chlamydia pneumoniae -Legionella pneumophila

-Mycoplasma pneumoniae
Viruses -Adenovirus
-Coronavirus
-Human Metapneumovirus
-Human Rhinovirus/Enterovirus
-Influenza A
-Influenza B
-Parainfluenza Virus
-Respiratory Syncytial Virus

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

Type of Use (Select one or both, as applicable)
-------------------------------------------------

✕ Prescription Use (Part 21 CFR 801 Subpart D)

| Over-The-Counter Use (21 CFR 801 Subpart C)

CONTINUE ON A SEPARATE PAGE IF NEEDED.

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Special 510(k) Summary BioFire Diagnostics, LLC

FilmArray Pneumonia Panel

Introduction:

Purpose

The content of this Special 510(k) submission is limited to obtaining FDA clearance for the FilmArray PN Panel (K180966) with modified labeling to address recent stability results of the adenovirus2 assay used for the detection of adenovirus C species.

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.

Background

Stability study results showed that the Adenovirus2 assay on the PN Panel exhibited an increased rate of unexpected Negative results in pouches that are more than 6 months from the date of manufacture (i.e. within 6 months of expiration). As a result of the stability testing, BioFire conducted a voluntary recall of the FilmArray PN Panel (Part No. RFIT-ASY-0144 and RFIT-ASY-0145) in June 2021 (refer to Recall Event 88117/ Z-2039-2021).

In addition, and as a corrective action, the FilmArray PN Panel 'Limitations' section in the Instructions for Use has been modified to include new limitations as well as an additional footnote on the analytical Limit of Detection (LoD) table (Table 62 in the Instructions for Use) that addresses the detection of adenovirus in the FilmArray PN Panel within 6 months of expiration.

Submitted by:

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

Contact:

Kevin Bourzac, Ph.D. Telephone: 801-736-6354, ext. 1358 Fax: 801-588-0507 Email: Kevin.bourzac@biofiredx.com

Date Submitted:

August 26, 2021

Trade Name: FilmArrav Pneumonia Panel

BioFire Diagnostics, LLC Special 510(k) FilmArray PN Panel Label Modification

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Classification Name:

Device to detect and identify microorganisms and associated resistance marker nucleic acids directly in respiratory specimens (21 CFR 866.3985)

Predicate Device:

K180966 – FilmArray Pneumonia (PN) Panel

Intended Use:

The FilmArray® Pneumonia Panel is a multiplexed nucleic acid test intended for use with FilmArray® 2.0 or FilmArray® Torch systems for the simultaneous detection and identification of multiple respiratory viral and bacterial nucleic acids, as well as select antimicrobial resistance genes, in sputum-like specimens (induced or expectorated sputum, or endotracheal aspirates) or bronchoalveolar lavage (BAL)-like specimens (BAL or mini-BAL) obtained from individuals suspected of lower respiratory tract infection.

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-baumanniicomplex	Klebsiella oxytoca	Serratia marcescens
Enterobacter cloacae complex	Klebsiella pneumoniaegroup	Staphylococcus aureus
Escherichia coli	Moraxella catarrhalis	Streptococcus agalactiae
Haemophilus influenzae	Proteus spp.	Streptococcus pneumoniae
Klebsiella aerogenes	Pseudomonas aeruginosa	Streptococcus pyogenes

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

Atypical Bacteria
Chlamydia pneumoniae	Legionella pneumophila	Mycoplasma pneumoniae
Viruses
Adenovirus	Human Rhinovirus/Enterovirus	Parainfluenza Virus
Coronavirus	Influenza A	Respiratory Syncytial Virus
Human Metapneumovirus	Influenza B
Antimicrobial Resistance Genes
CTX-M	NDM	mecA/C and MREJ
IMP	OXA-48-like
KPC	VIM

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The detection and identification of specific viral and bacterial nucleic acids, as well as the estimation of relative abundance of nucleic acid from common bacterial analytes, within specimens collected from individuals exhibiting signs and/or symptoms of a respiratory infection, aids in the diagnosis of lower respiratory infection if used in conjunction with other clinical and epidemiological information. The results of this test should not be used as the sole basis for diagnosis, treatment, or other patient management decisions.

Detection of bacterial nucleic acid may be indicative of colonizing or normal respiratory flora and may not indicate the causative agent of pneumonia. Semi-quantitative Bin (copies/mL) results generated by the FilmArray Pneumonia Panel are not equivalent to CFU/mL and do not consistently correlate with the quantity of bacterial analytes compared to CFU/mL. For specimens with multiple bacteria detected, the relative abundance of nucleic acids (copies/mL) may not correlate with the relative abundance of bacteria as determined by culture (CFU/mL). Clinical correlation is advised to determine significance of semi-quantitative Bin (copies/mL) for clinical management.

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.

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Device Description:

Bacteria - Quantitative Results	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
Staphylococcus aureus	Human Rhinovirus/Enterovirus
Streptococcus agalactiae	Influenza A
Streptococcus pneumoniae	Influenza B
Streptococcus pyogenes	Parainfluenza Virus
Bacteria (Atypical) - Qualitative Results	Respiratory Syncytial Virus
Chlamydia pneumoniae
Legionella pneumophila
Mycoplasma pneumoniae

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Device Comparison:

Table 1 outlines the similarities and differences between the two panels.

Element	Modified Device:FilmArray PN Panel (with modified labeling)	Predicate:FilmArray PN Panel(K180966)
OrganismsDetected	Bacteria: Acinetobacter calcoaceticus-baumanniicomplex, Enterobacter aerogenes, Enterobactercloacae complex, Escherichia coli, Haemophilusinfluenzae, Klebsiella oxytoca, Klebsiella	Same

		Table 1 Comparison of the FilmArray PN with modified labeling to the current FilmArray PN Panel.

BioFire Diagnostics, LLC Special 510(k) FilmArray PN Panel Label Modification

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Element	Modified Device:FilmArray PN Panel (with modified labeling)	Predicate:FilmArray PN Panel(K180966)
	pneumoniae group, Moraxella catarrhalis, Proteusspp., Pseudomonas aeruginosa, Serratia marcescens,Staphylococcus aureus, Streptococcus agalactiae,Streptococcus pneumoniae, Streptococcus pyogenes
	Atypical Bacteria: Chlamydia pneumoniae,Legionella pneumophila, Mycoplasma pneumoniae
	Antimicrobial Resistance Genes: CTX-M, IMP,KPC, mecA/C + MREJ, NDM, Oxa48-like, VIM
	Viruses: Adenovirus, Coronavirus, HumanMetapneumovirus, Human Rhinovirus/Enterovirus,Influenza A, Influenza B, Parainfluenza virus,
	Respiratory Syncytial virus
Analyte	DNA/RNA	Same
Specimen Types	Positive blood culture samples containing gram-positive or gram-negative bacteria and/or yeast.	Same
TechnologicalPrinciples	Nested multiplex PCR followed by high resolutionmelting analysis to confirm the identity of amplifiedproduct.	Same
Instrumentation	Single instrument FilmArray 2.0 System, orFilmArray Torch System	Same
Time to result	About 1 hour	Same
TestInterpretation	Automated test interpretation and report generation.User cannot access raw data.	Same
SamplePreparationMethod	Sample Processing is automated in the FilmArray PNpouch.	Same
Reagent Storage	Reagents are stored at room temperature.	Same
Shelf-Life	12 months from Date of Manufacture (DOM)*	Same
Controls	Two controls are included in each reagent pouch tocontrol for sample processing and both stages of PCRand melt analysis.	Same
UserComplexity	Moderate/Low	Same

LoD for adenovirus species C is 10 – 100 x impaired when pouches are within 6 months of expiration

The purpose of this submission is to modify the labeling of the FilmArray PN Panel to include the following limitations in the Instructions for Use:

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1. There is an increased risk of false negative Adenovirus results for adenovirus species C when using a pouch that is within 6 months of the expiration date due to a 10-100 x loss in sensitivity (i.e. impairment leading to an increase in the LoD). The test performance is not impacted if kits are more than 6 months from expiration date. Performance for other adenovirus species is not impacted.
1. If using a pouch that is within 6 months of expiration when a patient is suspected of adenovirus C infection, confirm all negative Adenovirus results using another method prior to reporting the result, or alternatively, do not report a negative Adenovirus result.

An additional footnote in the Analytical LoD (Table 62) of the Instructions for Use will also be included.

Conclusion:

The fundamental scientific technology, performance, and risk of the FilmArray PN Panel is unchanged from the legally marketed FilmArray PN Panel. There is no change to the product itself. only to the labeling (Instructions for Use). Therefore, the modified FilmArray PN Panel performs as well as the predicate device.

Regulation Number and Section

§ 866.3985 Device to detect and identify microorganisms and associated resistance marker nucleic acids directly in respiratory specimens.

(a)
Identification. A device to detect and identify microorganisms and associated resistance marker nucleic acids directly from respiratory specimens is an in vitro diagnostic device intended for the detection and identification of microorganisms and associated resistance markers in respiratory specimens collected from patients with signs or symptoms of respiratory infection. The device is intended to aid in the diagnosis of respiratory infection in conjunction with clinical signs and symptoms and other laboratory findings. These devices do not provide confirmation of antibiotic susceptibility since mechanisms of resistance may exist other than those detected by the device.(b)
Classification. Class II (special controls). The special controls for this device are:(1) The intended use for the 21 CFR 809.10 labeling must include a detailed description of what the device detects, the type of results provided to the user, the clinical indications appropriate for test use, and the specific population(s) for which the device is intended.
(2) The 21 CFR 809.10(b) labeling must include:
(i) A detailed device description, including all device components, control elements incorporated into the test procedure, instrument requirements, ancillary reagents required but not provided, and a detailed explanation of the methodology, including all pre-analytical methods for processing of specimens.
(ii) Performance characteristics from analytical studies, including, but not limited to, limit of detection, inclusivity, reproducibility, cross reactivity, interfering substances, competitive inhibition, carryover/cross contamination, specimen stability, and linearity, as applicable.
(iii) A limiting statement that the device is intended to be used in conjunction with clinical history, signs and symptoms, and results of other diagnostic tests, including culture and antimicrobial susceptibility testing.
(iv) A detailed explanation of the interpretation of test results for clinical specimens and acceptance criteria for any quality control testing.
(v) A limiting statement that negative results for microorganisms do not preclude the possibility of infection, and should not be used as the sole basis for diagnosis, treatment, or other patient management decisions.
(vi) If applicable, a limiting statement that detected microorganisms may not be the cause of lower respiratory tract infection and may be indicative of colonizing or normal respiratory flora.
(vii) If applicable, a limiting statement that detection of resistance markers cannot be definitively linked to specific microorganisms and that the source of a detected resistance marker may be an organism not detected by the assay, including colonizing flora.
(viii) If applicable, a limiting statement that detection of antibiotic resistance markers may not correlate with phenotypic gene expression.
(3) The 21 CFR 809.10(b) labeling and any test report generated by the device must include a limiting statement that negative results for resistance markers do not indicate susceptibility of detected microorganisms.
(4) Design verification and validation must include:
(i) Performance characteristics from clinical studies that include prospective (sequential) samples and, if appropriate, additional characterized samples. The study must be performed on a study population consistent with the intended use population and compare the device performance to results obtained from an FDA accepted reference method and/or FDA accepted comparator method, as appropriate. Results from the clinical studies must include the clinical study protocol (including predefined statistical analysis plan, if applicable), clinical study report, and results of all statistical analyses.
(ii) A detailed device description including the following:
(A) Thorough description of the assay methodology including, but not limited to, primer/probe sequences, primer/probe design, and rationale for target sequence selection, as applicable.
(B) Algorithm used to generate a final result from raw data (e.g., how raw signals are converted into a reported result).
(iii) A detailed description of device software, including, but not limited to, validation activities and outcomes.
(iv) As part of the risk management activities, an appropriate end user device training program must be offered as an effort to mitigate the risk of failure from user error.