Predicate Devices

Reference Devices

Not Found

AI/ML (Artificial Intelligence / Machine Learning)

No
The description focuses on the biochemical and mechanical processes of nucleic acid detection and PCR, with software interpreting melt curve analysis. There is no mention of AI/ML algorithms for image analysis or result interpretation beyond standard melt curve analysis.

Therapeutic

No
Explanation: The device is an in vitro diagnostic test for detecting nucleic acids from various pathogens in stool samples, aiding in the diagnosis of gastrointestinal illness. It does not directly provide therapy or treatment.

Diagnostic

Yes

The text explicitly states that the FilmArray Gastrointestinal (GI) Panel is an "in vitro diagnostic test" and is "indicated as an aid in the diagnosis of gastrointestinal illness."

SaMD (Software as a Medical Device)

No

The device description explicitly details hardware components including the FilmArray instrument, pouches containing reagents, inflatable bladders, seal points, pneumatic pistons, Peltier devices, and a digital camera. While software is used for interpretation, it is integral to a system that includes significant hardware.

IVD (In Vitro Diagnostic)

Based on the provided text, the device is explicitly described as an in vitro diagnostic (IVD).

Here's why:

Intended Use / Indications for Use: The very first sentence states, "The FilmArray Gastrointestinal (GI) Panel is a qualitative multiplexed in vitro diagnostic test intended for use with FilmArray systems."
Purpose: The intended use clearly describes the device's purpose as detecting and identifying nucleic acids from various pathogens in stool samples to aid in the diagnosis of gastrointestinal illness. This is a core function of an IVD.
Sample Type: It uses biological samples (stool) obtained from individuals.
Analysis: It performs analysis on these samples (nucleic acid detection and identification).
Clinical Context: The results are intended to be used in conjunction with other clinical data to aid in diagnosis.

Therefore, there is no ambiguity; the device is an IVD.

PCCP (Predetermined Change Control Plan) Authorized

N/A

Overview

Intended Use / Indications for Use

The FilmArray Gastrointestinal (GI) Panel is a qualitative multiplexed in vitro diagnostic test intended for use with FilmArray systems. The FilmArray GI Panel is capable of the simultaneous detection and identification of nucleic acids from multiple bacteria, viruses, and parasites directly from stool samples in Cary Blair transport media obtained from individuals with signs and/or symptoms of gastrointestinal infection. The following bacteria (including several diarrheagenic E. coli/Shigella pathotypes), parasites, and viruses are identified using the FilmArray GI Panel:

Campylobacter (C. jejuni/C. coli/C. upsaliensis)
Clostridium difficile (C. difficile) toxin A/B
Plesiomonas shigelloides
Salmonella
Vibrio (V. parahaemolyticus/V. cholerae) including specific identification of Vibrio cholerae
Yersinia enterocolitica
Enteroaggregative Escherichia coli (EAEC)
Enteropathogenic Escherichia coli (EPEC)
Enterotoxigenic Escherichia coli (ETEC) lt/st
Shiga-like toxin-producing Escherichia coli (STEC) stx1/stx2 (including specific identification of the E. coli O157 serogroup within STEC)
Shigella/Enteroinvasive Escherichia coli (EIEC)
Cryptosporidium
Cyclospora cayetanensis
Entamoeba histolytica
Giardia lamblia (also known as G. intestinalis and G. duodenalis)
Adenovirus F 40/41
Astrovirus
Norovirus GI/GII
Rotavirus A
Sapovirus (Genogroups I, II, IV, and V)

The FilmArray GI Panel is indicated as an aid in the diagnosis of gastrointestinal illness and results are meant to be used in conjunction with other clinical, laboratory, and epidemiological data. Positive results do not rule out co-infection with organisms not included in the FilmArray GI Panel. The agent detected may not be the definite cause of the disease.

Concomitant culture is necessary for organism recovery and further typing of bacterial agents.

This device is not intended to monitor or guide treatment for C. difficile infection.

Due to the small number of positive specimens collected for certain organisms during the prospective clinical study, performance characteristics for E. coli O157, Plesiomonas shigelloides, Yersinia enterocolitica, Astrovirus, and Rotavirus A were established primarily with retrospective clinical specimens.

Performance characteristics for Entamoeba histolytica, and Vibrio (V. parahaemolyticus, V. vulnificus, and Vibrio cholerae) were established primarily using contrived clinical specimens.

Negative FilmArray GI Panel results in the setting of clinical illness compatible with gastroenteritis may be due to infection by pathogens that are not detected by this test or non-infectious causes such as ulcerative colitis, irritable bowel syndrome, or Crohn's disease.

A gastrointestinal microorganism multiplex nucleic acid-based assay also aids in the detection and identification of acute gastroenteritis in the context of outbreaks.

Product codes (comma separated list FDA assigned to the subject device)

PCH, OOI

Device Description

The FilmArray Gastrointestinal (GI) Panel is a multiplex nucleic acid test designed to be used with FilmArray systems. The FilmArray GI pouch contains freeze-dried reagents to perform nucleic acid purification and nested, multiplex PCR with DNA melt analysis. The FilmArray Gastrointestinal (GI) Panel simultaneously conducts 22 tests for the identification of GI pathogens from stool specimens collected in Cary Blair transport medium (Table 1). Results from the FilmArray GI Panel test are available within about one hour.

A test is initiated by loading Hydration Solution into one port of the FilmArray pouch and a stool sample (in Cary Blair transport medium) mixed with the provided Sample Buffer into the other port of the FilmArray GI pouch and placing it in the 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/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, a nested multiplex PCR is executed in two stages. During the first stage, a single, large volume, highly multiplexed reverse transcription PCR (rt-PCR) reaction is performed. 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 Defense, LLC). 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 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 array captures fluorescent images of the PCR2 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.

Mentions image processing

Yes

Mentions AI, DNN, or ML

Not Found

Input Imaging Modality

Not Found

Anatomical Site

Gastrointestinal

Indicated Patient Age Range

Not Found

Intended User / Care Setting

Not Found

Description of the training set, sample size, data source, and annotation protocol

Not Found

Description of the test set, sample size, data source, and annotation protocol

Clinical Performance Study:
Specimens previously obtained during the FilmArray GI prospective clinical evaluation comprised the base of the specimen set used for testing. This set was supplemented with other archived specimens collected from external medical facilities and reference laboratories to increase the number of specimens being tested for low prevalence analytes. Contrived clinical specimens were also used for GI analytes which are rare (Entamoeba histolytica, Vibrio spp., and V. cholerae). A total of 104 specimens were selected such that each analyte was represented 3-5 times.

Low Analyte Study:
Testing consisted of a titration of samples containing GI Panel analytes at concentrations above, at, and below (10x, 1x, 0.1x and 0.01x) LoD. Additional side-by-side testing at and near LoD (20 replicates on each system).

Reproducibility Study:
A panel of contrived stool samples, each spiked with various concentrations of five different GI Panel analytes. Each analyte was evaluated at three different concentrations (Negative, Low Positive and Moderate Positive). Samples were stored refrigerated (4°C) and tested on four different days at three testing sites (one system, A, B, or C per site) for 108 data points per sample.

Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)

Clinical Performance:
Study Type: Clinical Study comparing performance between the current FilmArray system and FilmArray 2.0.
Sample Size: 104 specimens for the main comparison.
Key Results:

System performance for the current system: 104/105 runs completed (99.0%). No control failures.
System performance for the modified system: 104/104 runs attempted, all completed (100%). One control failure.
100% concordance observed for 14/22 analytes between systems.
For PPA, 19/22 analytes were 100% concordant.
For NPA, 15/22 analytes were 100% concordant.
Overall PPA was 96.4% (95% CI: 91.0-100%).
Overall NPA was 99.4% (95% CI: 98.9-100%).

Low Analyte Study:
Study Type: Analytic Study comparing performance at low analyte levels between systems.
Sample Size: 20 replicates on each system for testing at LoD.
Key Results:

In titration series testing, amplification and detection of each analyte were comparable between systems at all concentrations.
Testing of additional replicates at LoD showed equivalent detection on both systems (>95% agreement between current and modified and/or overlapping 2-sided 95% confidence intervals).
Mean Tm values for all FilmArray GI Panel assays on the modified system were ± 0.4°C or less compared to the same samples tested on the current system (△Tm).

Reproducibility Study:
Study Type: Multicenter Reproducibility Study.
Sample Size: 108 data points per sample (36 replicates per site x 3 sites).
Key Results:

The test results obtained for the Gastrointestinal Panel on the FilmArray 2.0 were highly reproducible and consistent with data collected on the current FilmArray.
Overall % Agreement with Expected Results (All Sites/Systems) for the multi-instrument FilmArray System:
- Clostridium difficile (Moderate Positive): 100% (95% CI: 96.6-100%)
- Clostridium difficile (Low Positive): 99.1% (95% CI: 95.0-100%)
- Clostridium difficile (Negative): 100% (95% CI: 96.6-100%)
- Shiga-toxin producing Escherichia coli (STEC O157) (Moderate Positive): 100% (95% CI: 96.6-100%)
- Shiga-toxin producing Escherichia coli (STEC O157) (Low Positive): 100% (95% CI: 96.6-100%)
- Shiga-toxin producing Escherichia coli (STEC O157) (Negative): 100% (95% CI: 96.6-100%)
- Cryptosporidium parvum (Moderate Positive): 100% (95% CI: 96.6-100%)
- Cryptosporidium parvum (Low Positive): 99.1% (95% CI: 95.0-100%)
- Cryptosporidium parvum (Negative): 100% (95% CI: 96.6-100%)
- Adenovirus F41 (Moderate Positive): 100% (95% CI: 96.6-100%)
- Adenovirus F41 (Low Positive): 100% (95% CI: 96.6-100%)
- Adenovirus F41 (Negative): 100% (95% CI: 96.6-100%)
- Astrovirus (Moderate Positive): 100% (95% CI: 96.6-100%)
- Astrovirus (Low Positive): 100% (95% CI: 96.6-100%)
- Astrovirus (Negative): 100% (95% CI: 96.6-100%)
Tm reproducibility was also evaluated, and standard deviations were generally low (e.g., ± 0.1 to ± 0.6).

Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)

Clinical Performance:

Overall PPA: 96.4%
Overall NPA: 99.4%

Predicate Device(s): If the device was cleared using the 510(k) pathway, identify the Predicate Device(s) K/DEN number used to claim substantial equivalence and list them here in a comma separated list exactly as they appear in the text. List the primary predicate first in the list.

K140407

Reference Device(s): Identify the Reference Device(s) K/DEN number and list them here in a comma separated list exactly as they appear in the text.

Not Found

Predetermined Change Control Plan (PCCP) - All Relevant Information for the subject device only (e.g. presence / absence, what scope was granted / cleared under the PCCP, any restrictions, etc).

Not Found

Regulation Number and Section

§ 866.3990 Gastrointestinal microorganism multiplex nucleic acid-based assay.

(a)
Identification. A gastrointestinal microorganism multiplex nucleic acid-based assay is a qualitativein vitro diagnostic device intended to simultaneously detect and identify multiple gastrointestinal microbial nucleic acids extracted from human stool specimens. The device detects specific nucleic acid sequences for organism identification as well as for determining the presence of toxin genes. The detection and identification of a specific gastrointestinal microbial nucleic acid from individuals exhibiting signs and symptoms of gastrointestinal infection aids in the diagnosis of gastrointestinal infection when used in conjunction with clinical evaluation and other laboratory findings. A gastrointestinal microorganism multiplex nucleic acid-based assay also aids in the detection and identification of acute gastroenteritis in the context of outbreaks.(b)
Classification. Class II (special controls). The special controls are set forth in FDA's guideline document entitled: “Class II Special Controls Guideline: Gastrointestinal Microorganism Multiplex Nucleic Acid-Based Assays for Detection and Identification of Microorganisms and Toxin Genes from Human Stool Specimens.” For availability of the guideline document, see § 866.1(e).

Summary

0

Image /page/0/Picture/1 description: The image shows the logo for the Department of Health & Human Services - USA. The logo features a stylized caduceus symbol, which is a staff entwined by two snakes, often associated with medicine and healthcare. The text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" is arranged in a circular pattern around the symbol.

Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002

BIOFIRE DIAGNOSTICS, LLC KRISTEN KANACK, PHD VICE PRESIDENT OF REGULATED PRODUCTS 390 WAKARA WAY SALT LAKE CITY UT 84108

February 19, 2015

Re: K143005

Trade/Device Name: FilmArrav Gastrointestinal (GI) Panel for use with the FilmArray 2.0 Regulation Number: 21 CFR 866.3990 Regulation Name: Gastrointestinal microorganism multiplex nucleic acid-based assay Regulatory Class: II Product Code: PCH, OOI Dated: January 15, 2015 Received: January 20, 2015

Dear Dr. 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. 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 Parts 801 and 809); medical device reporting (reporting of medical device-related adverse events) (21 CFR 803); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

1

If you desire specific advice for your device on our labeling regulations (21 CFR Parts 801 and 809), please contact the Division of Industry and Consumer Education at its toll-free number (800) 638 2041 or (301) 796-7100 or at its Internet address

http://www.fda.gov/MedicalDevices/Resourcesfor You/Industry/default.htm. 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 the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance.

You may obtain other general information on your responsibilities under the Act from the Division of Industry and Consumer Education at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address

http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm.

Sincerely yours,

Uwe Scherf - S for

Sally Hojvat, M. Sc., Ph.D. Director Division of Microbiology Devices Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health

Enclosure

2

Indications for Use

510(k) Number (if known) K143005

Device Name FilmArray Gastrointestinal (GI) Panel

Indications for Use (Describe)

The FilmArray Gastrointestinal (GI) Panel is a qualitative multiplexed in vitro diagnostic test intended for use with FilmArray systems. The FilmArray GI Panel is capable of the simultaneous detection and identification of nucleic acids from multiple bacteria, viruses, and parasites directly from stool samples in Cary Blair transport media obtained from individuals with signs and/or symptoms of gastrointestinal infection. The following bacteria (including several diarrheagenic E. coli/Shigella pathotypes), parasites, and viruses are identified using the FilmArray GI Panel:

· Campylobacter (C. jejuni/C. coli/C. upsaliensis)
· Clostridium difficile (C. difficile) toxin A/B
Plesiomonas shigelloides
· Salmonella
· Vibrio (V. parahaemolyticus/V. cholerae) including specific identification of Vibrio cholerae
· Yersinia enterocolitica
· Enteroaggregative Escherichia coli (EAEC)
· Enteropathogenic Escherichia coli (EPEC)
· Enterotoxigenic Escherichia coli (ETEC) lt/st
· Shiga-like toxin-producing Escherichia coli (STEC) stx1/stx2 (including specific identification of the E. coli 0157 serogroup within STEC)
· Shigella/Enteroinvasive Escherichia coli (EIEC)
· Cryptosporidium
· Cyclospora cayetanensis
Entamoeba histolytica
· Giardia lamblia (also known as G. intestinalis and G. duodenalis)
· Adenovirus F 40/41
Astrovirus
Norovirus GI/GII
Rotavirus A
· Sapovirus (Genogroups I, II, IV, and V)

The FilmArray GI Panel is indicated as an aid in the diagnosis of gastrointestinal illness and results are meant to be used in conjunction with other clinical, laboratory, and epidemiological data. Positive results do not rule out co-infection with organisms not included in the FilmArray GI Panel. The agent detected may not be the definite cause of the disease.

Concomitant culture is necessary for organism recovery and further typing of bacterial agents.

This device is not intended to monitor or guide treatment for C. difficile infection.

Due to the small number of positive specimens collected for certain organisms during the prospective clinical study,

performance characteristics for E. coli 0157, Plesiomonas shigelloides, Yersinia enterocolitica, Astrovirus, and Rotavirus A were established primarily with retrospective clinical specimens.

Performance characteristics for Entamoeba histolytica, and Vibrio (V. parahaemolyticus, V. vulnificus, and Vibrio cholerae) were established primarily using contrived clinical specimens.

Negative FilmArray GI Panel results in the setting of clinical illness compatible with gastroenteritis may be due to infection by pathogens that are not detected by this test or non-infectious causes such as ulcerative colitis, irritable bowel syndrome, or Crohn's disease.

A gastrointestinal microorganism multiplex nucleic acid-based assay also aids in the detection and identification of acute

3

gastroenteritis in the context of outbreaks.

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

X 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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DO NOT SEND YOUR COMPLETED FORM TO THE PRA STAFF EMAIL ADDRESS BELOW.

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"An agency may not conduct or sponsor, and a person is not required to respond to, a collection of information unless it displays a currently valid OMB number."

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510(k) Summary BioFire Diagnostics, LLC

FilmArray Gastrointestinal (GI) Panel for use with FilmArray 2.0

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 390 Wakara Way Salt Lake City, UT 84108 USA

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

Contact: Kristen Kanack, ext. 330

Date Submitted: October 17, 2014

Device Name and Classification:

Trade Name: FilmArray Gastrointestinal (GI) Panel

Regulation Number: 21 CFR 866.3990

Classification Name: Gastrointestinal microorganism multiplex nucleic acid-based assay

Predicate Device:

K 140407 - FilmArray GI Panel

Intended Use:

The FilmArray Gastrointestinal (GI) Panel is a qualitative multiplexed nucleic acid-based in vitro diagnostic test intended for use with FilmArray systems. The FilmArray GI Panel is capable of the simultaneous detection and identification of nucleic acids from multiple bacteria, viruses, and parasites directly from stool samples in Cary Blair transport media obtained from individuals with signs and/or symptoms of gastrointestinal infection. The following bacteria (including several diarrheagenic E. coli/Shigella pathotypes), parasites, and viruses are identified using the FilmArray GI Panel:

Campylobacter (C. jejuni/C. coli/C. upsaliensis)
Clostridium difficile (C. difficile) toxin A/B ●
Plesiomonas shigelloides .

BioFire Diagnostics, LLC 510(k) Multi-instrument FilmArray Gastrointestinal Panel

5

Salmonella
Vibrio (V. parahaemolyticus/V. vulnificus/V. cholerae) including specific identification of Vibrio cholerae
Yersinia enterocolitica ●
Enteroaggregative Escherichia coli (EAEC)
Enteropathogenic Escherichia coli (EPEC) ●
Enterotoxigenic Escherichia coli (ETEC) lt/st ●
Shiga-like toxin-producing Escherichia coli (STEC) stx1/stx2 (including specific ● identification of the E. coli 0157 serogroup within STEC)
Shigella/Enteroinvasive Escherichia coli (EIEC)
Cryptosporidium
Cyclospora cayetanensis
Entamoeba histolytica
Giardia lamblia (also known as G. intestinalis and G. duodenalis)
Adenovirus F 40/41
Astrovirus
Norovirus GI/GII
Rotavirus A ●
. Sapovirus (Genogroups I, II, IV, and V)

The FilmArray GI Panel is indicated as an aid in the diagnosis of specific agents of gastrointestinal illness and results are meant to be used in conjunction with other clinical, laboratory, and epidemiological data. Positive results do not rule out co-infection with organisms not included in the FilmArray GI Panel. The agent detected may not be the definite cause of the disease.

Concomitant culture is necessary for organism recovery and further typing of bacterial agents.

This device is not intended to monitor or guide treatment for C. difficile infection.

Due to the small number of positive specimens collected for certain organisms during the prospective clinical study, performance characteristics for E. coli O157, Plesiomonas shigelloides, Yersinia enterocolitica, Astrovirus, and Rotavirus A were established primarily with retrospective clinical specimens.

Performance characteristics for Entamoeba histolytica, and Vibrio (V. parahaemolyticus, V. vulnificus, and Vibrio cholerae) were established primarily using contrived clinical specimens.

Negative FilmArray GI Panel results in the setting of clinical illness compatible with gastroenteritis may be due to infection by pathogens that are not detected by this test or noninfectious causes such as ulcerative colitis, irritable bowel syndrome, or Crohn's disease.

A gastrointestinal microorganism multiplex nucleic acid-based assay also aids in the detection and identification of acute gastroenteritis in the context of outbreaks.

6

Device Description:

The FilmArray Gastrointestinal (GI) Panel is a multiplex nucleic acid test designed to be used with FilmArray systems. The FilmArray GI pouch contains freeze-dried reagents to perform nucleic acid purification and nested, multiplex PCR with DNA melt analysis. The FilmArray Gastrointestinal (GI) Panel simultaneously conducts 22 tests for the identification of GI pathogens from stool specimens collected in Cary Blair transport medium (Table 1). Results from the FilmArray GI Panel test are available within about one hour.

Bacteria	Viruses
Campylobacter (C. jejuni/C. coli/C. upsaliensis)	Adenovirus F 40/41
Clostridium difficile (toxin A/B)	Astrovirus
Plesiomonas shigelloides	Norovirus GI/GII
Salmonella	Rotavirus A
Vibrio(V. parahaemolyticus/V. vulnificus/V. cholerae)	Sapovirus (Genogroups I, II, IV, and V)
Vibrio cholerae
Yersinia enterocolitica
Diarrheagenic E. coli/Shigella	Parasites
Enteroaggregative E. coli (EAEC)	Cryptosporidium
Enteropathogenic E. coli (EPEC)	Cyclospora cayetanensis
Enterotoxigenic E. coli (ETEC) lt/st	Entamoeba histolytica
Shiga toxin-producing E. coli (STEC) stx1/stx2	Giardia lamblia
E. coli O157
Shigella/Enteroinvasive E. coli (EIEC)

Table 1. Bacteria, Viruses, Diarrheagenic E. coli/Shigella, and Parasites Detected by the FilmArray GI Panel

A test is initiated by loading Hydration Solution into one port of the FilmArray pouch and a stool sample (in Cary Blair transport medium) mixed with the provided Sample Buffer into the other port of the FilmArray GI pouch and placing it in the 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/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

7

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, a nested multiplex PCR is executed in two stages. During the first stage, a single, large volume, highly multiplexed reverse transcription PCR (rt-PCR) reaction is performed. 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 Defense, LLC). 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 each well of the array. At the conclusion of the 240 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 array captures fluorescent images of the PCR2 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.

Substantial Equivalence:

The FilmArray GI Panel for use with FilmArray 2.0 is substantially equivalent to the FilmArray GI Panel (K140407), which was cleared for use with the FilmArray on May 2, 2014 and determined to be a Class II device.

The following table compares the FilmArray GI Panel for use with FilmArray 2.0 to the previously cleared FilmArray GI Panel (K140407). The table outlines the similarities and differences for the GI Panel tested on the two devices.

8

FilmArray(Predicate).
Element	Predicate:
FilmArray Gastrointestinal Panel
(K140407)	New Device:
FilmArray Gastrointestinal Panel for use
with FilmArray 2.0
Organisms
Detected	Campylobacter (C. jejuni/C. coli/C.
upsaliensis), Clostridium difficile (C.
difficile) toxin A/B, Plesiomonas
shigelloides, Salmonella, Vibrio (V.
parahaemolyticus/V. vulnificus/V. cholerae)
including specific identification of Vibrio
cholera, Yersinia enterocolitica,
Enteroaggregative Escherichia coli
(EAEC), Enteropathogenic Escherichia coli
(EPEC), Enterotoxigenic Escherichia coli
(ETEC) lt/st, Shiga-like toxin-producing
Escherichia coli (STEC) stx1/stx2
(including specific identification of the E.
coli O157 serogroup within STEC),
Shigella/Enteroinvasive Escherichia coli
(EIEC),Cryptosporidium, Cyclospora
cayetanensis, Entamoeba histolytica,
Giardia lamblia (also known as G.
intestinalis and G. duodenalis), Adenovirus
F 40/41, Astrovirus, Norovirus GI/GII,
Rotavirus A, and Sapovirus (Genogroups I,
II, IV, and V).	Same
Analyte	RNA/DNA	Same
Specimen Types	Human stool in Cary Blair transport
medium	Same
Technological
Principles	Nested multiplex RT-PCR followed by high
resolution melting analysis to confirm
identity of amplified product.	Same
Instrumentation	FilmArray	FilmArray or FilmArray 2.0
Time to result	About 1 hour	Same
Test
Interpretation	Automated test interpretation and report
generation. User cannot access raw data.	Same
Sample
Preparation
Method	Sample Processing is automated in the
FilmArray GI pouch.	Same
Reagent Storage	Reagents are stored at room temperature.	Same
Controls	Two controls are included in each reagent
pouch to control for sample processing and
both stages of PCR and melt analysis.	Same
User
Complexity	Moderate/Low	Same

Table 2. Comparison of the FilmArray GI Panel on FilmArray 2.0 to the FilmArray GI Panel on the FilmArray(Predicate).

Summary of Performance Data

9

Clinical Performance

The original FilmArray GI Panel was developed for use with the current, single instrument FilmArray. A clinical study was conducted to compare the performance observed when testing clinical specimens using the GI Panel on the current system to results obtained when testing with the modified system (FilmArray 2.0).

Specimens previously obtained during the FilmArray GI prospective clinical evaluation comprised the base of the specimen set used for testing. This set was supplemented with other archived specimens collected from external medical facilities and reference laboratories to increase the number of specimens being tested for low prevalence analytes. Contrived clinical specimens were also used for GI analytes which are rare (Entamoeba histolytica, Vibrio spp., and V. cholerae). A total of 104 specimens were selected such that each analyte was represented 3-5 times.

System performance for testing these 104 specimens on each platform was calculated. For the current system, a total of 105 runs were attempted, 104 of which were completed (99.0%; 104/105). One run was aborted by the user (0.9%). No control failures were observed.

For the modified system, a total of 104 runs were attempted, all of which were completed (100%; 104/104). There was one control failure. One norovirus specimen was excluded following the control failure due to insufficient specimen volume for retesting.

As shown in Table 3, 100% concordance was observed for most analytes (14/22) between the current and modified system. For PPA, 19/22 analytes were 100% concordant, and for NPA, 15/22 analytes were 100% concordant. Occasional discrepant results were observed where an analyte was detected by one out of two pouches; in many cases this was attributed to analyte levels below the limit of detection (LoD) in specimens that had previously been characterized as positive for the discrepant analyte. Overall PPA was 96.4% with the lower bound of the twosided 95% confidence interval (95% CI) at 91.0%. Overall NPA was 99.4% with the lower bound of the two-sided 95% CI at 98.9 %.

	MS vs CS
Analyte	PPA	%	NPA	%
Bacteria
Campylobacter	5/5	100%	96/97a	99.0%
Clostridium difficile toxin A/B	5/5	100%	95/97b	97.9%
Plesiomonas shigelloides	3/3	100%	99/99	100%
Salmonella	5/5	100%	97/97	100%
Vibrio	6/7c	85.7%	94/95c	98.9%
Vibrio cholerae	3/3	100%	98/99c	99.0%
Yersinia enterocolitica	4/4	100%	98/98	100%
Diarrheagenic E. coli / Shigella
Enteroaggregative E. coli (EAEC)	8/8	100%	94/94	100%

Table 3. Analyte Detections for Modified vs. Current System, where results from the Current System are shown as the denominator. Comparisons demonstrating performance less than 100% but are shaded in yellow. CS = Current System, MS = Modified System

10

Analyte	MS vs CS
	PPA	%	NPA	%
Enteropathogenic E. coli (EPEC)	11/12d	91.7%	84/84	100%
Enterotoxigenic E. coli (ETEC)	5/5	100%	96/97e	99.0%
Shiga-like toxin-producing E. coli (STEC)	6/6	100%	96/96	100%
Escherichia coli O157	3/3	100%	3/3	100%
Shigella/Enteroinvasive E. coli (EIEC)	6/6	100%	96/96	100%
Parasites
Cryptosporidium	6/6	100%	96/96	100%
Cyclospora cayetanensis	4/4	100%	98/98	100%
Entamoeba histolytica	5/5	100%	97/97	100%
Giardia lamblia	6/6	100%	96/96	100%
Viruses
Adenovirus F 40/41	7/9f	77.8%	90/93f	96.8%
Astrovirus	5/5	100%	97/97	100%
Norovirus GI/GII	4/4	100%	96/98g	98.0%
Rotavirus A	4/4	100%	98/98	100%
Sapovirus	5/5	100%	97/97	100%
Overall agreement/	116/120	96.7%	2011/2022	99.5%
95% CI	91.7-99.1%		99.0-99.7%

a Campylobacter was detected in specimen 014111-GI-0028 when tested on the Modified System but was not detected when tested on the Current System. This specimen was originally characterized as positive for Campylobacter.

8 Specimens 014111-GI-0039 and 014111-GI-0060 were positive for C. difficile when tested with the Modified System but were not detected on the Current System. Both specimens were originally characterized as positive for C. difficile.

S Vibrio was detected in specimen 014111-GI-0106 when tested on the Current System but was not detected when tested on the Modified System. V. cholerae was detected with the Vchol assay in specimen 014111-GI-0108 when tested with the Modified System but not the Current System; a positive result of with the Vchol assay also resulted in a metacall for Vibrio. Both of these specimens were contrived specimens that had been spiked with Vibrio organism.

a EPEC was detected in specimen 014111-GI-0007 when tested on the Current System but was not detected when tested on the Modified System. EPEC had not been reported in this specimen by the source laboratory.

6 ETEC was detected by one of three ETEC assays in specimen 014111-GI-0015 when tested on the Modified System but not on the Current System. ETEC had not been reported in this specimen by the source laboratory. Adenovirus F 40/41 was alternately detected in five specimens (014111-GI-0080, 014111-GI-0085, 014111-GI-0088, and 14111-GI-0094) by the Current and Modified systems. Adenovirus F 40/41 had not been reported in any of these specimens by the source laboratory.

8 Specimens 014111-GI-0022 and 014111-GI-0086 were positive for Norovirus GI/GII when tested with the Modified System but were not detected on the Current System. Specimen 014111-GI-0022 was originally characterized as positive for Norovirus GI/GII, but specimen 014111-GI-0086 was not.

Selected Analytic Studies

11

Low Analyte

A comparison of performance at low analyte levels between the current FilmArray system (one instrument to one computer configuration) and the FilmArray 2.0 system (modified; up to eight instruments to one computer) was performed for the FilmArray Gastrointestinal (GI) Panel. The purpose of the testing was to determine whether detection of GI Panel analytes is equivalent between the systems.

Testing consisted of a titration of samples containing GI Panel analytes at concentrations above, at, and below (10x, 1×, 0.1× and 0.01×) LoD. Additional side-by-side testing at and near LoD (20 replicates on each system) was performed to further demonstrate consistency between the current and modified systems.

In the titration series testing, amplification, and detection of each analyte was found to be comparable between systems at all concentrations. Testing of additional replicates at LoD (Table 4) also revealed equivalent detection on both systems (>95% agreement between current and modified and/or overlapping 2-sided 95% confidence intervals).

| GI Panel Test Result | Species/Isolate | Current System
#Detected/Total
(% Detected)
[95% CI] | Modified System
#Detected/Total
(% Detected)
[95% CI] | Agreement
Between
Systems |
|---------------------------------------|----------------------------------------|---------------------------------------------------------------|----------------------------------------------------------------|---------------------------------|
| Bacteria | | | | |
| Campylobacter | Campylobacter jejuni | 20/20
(100%)
[83.2% - 100%] | 20/20
(100%)
[83.2% - 100%] | 100% |
| Clostridium difficile
toxin A/B | Clostridium difficile | 20/20
(100%)
[83.2% - 100%] | 19/20
(95%)
[75.1% - 99.9%] | 95% |
| Plesiomonas shigelloides | Plesiomonas shigelloides | 20/20
(100%)
[83.2% - 100%] | 20/20
(100%)
[83.2% - 100%] | 100% |
| Salmonella | Salmonella enterica
subsp. enterica | 20/20
(100%)
[83.2% - 100%] | 20/20
(100%)
[83.2% - 100%] | 100% |
| Vibrio/Vibrio cholerae | Vibrio cholerae | 40/40a
(100%)
[91.2% - 100%] | 37/40a
(92.5%)
[79.6% - 98.4%] | 96% |
| Vibrio | Vibrio parahaemolyticus | 40/40a
(100%)
[91.2% - 100%] | 37/40a
(92.5%)
[79.6% - 98.4%] | 96% |
| Yersinia enterocolitica | Yersinia enterocolitica | 20/20
(100%)
[83.2% - 100%] | 20/20
(100%)
[83.2% - 100%] | 100% |
| Diarrheagenic E. coli/Shigella | | | | |
| Enteroaggregative E. coli
(EAEC) | Escherichia coli (EAEC) | 20/20
(100%)
[83.2% - 100%] | 20/20
(100%)
[83.2% - 100%] | 100% |

Table 4. Results of Replicate Testing at LoD for the Gastrointestinal (GI) Panel on Current and Modified
FilmArrav Systems

12

| GI Panel Test Result | Species/Isolate | Current System
#Detected/Total
(% Detected)
[95% CI] | Modified
System
#Detected/Total
(% Detected)
[95% CI] | Agreement
Between
Systems |
|------------------------------------------------------------------------|-------------------------|---------------------------------------------------------------|-------------------------------------------------------------------|---------------------------------|
| Enteropathogenic E. coli
(EPEC) | Escherichia coli (EPEC) | 20/20
(100%)
[83.2% - 100%] | 20/20
(100%)
[83.2% - 100%] | 100% |
| Enterotoxigenic E. coli
(ETEC) It/st | Escherichia coli (ETEC) | 20/20
(100%)
[83.2% - 100%] | 20/20
(100%)
[83.2% - 100%] | 100% |
| Shiga-like toxin-producing
E. coli (STEC) stx1/stx2 | Escherichia coli (STEC) | 20/20
(100%)
[83.2% - 100%] | 20/20
(100%)
[83.2% - 100%] | 100% |
| Shiga-like toxin-producing
E. coli (STEC) stx1/stx2
E. coli O157 | Escherichia coli O157 | 20/20
(100%)
[83.2% - 100%] | 20/20
(100%)
[83.2% - 100%] | 100% |
| Shigella/Enteroinvasive | Escherichia coli (EIEC) | 20/20
(100%)
[83.2% - 100%] | 20/20
(100%)
[83.2% - 100%] | 100% |
| E. coli (EIEC) | Shigella sonnei | 20/20
(100%)
[83.2% - 100%] | 20/20
(100%)
[83.2% - 100%] | 100% |
| | Parasites | | | |
| Cryptosporidium | Cryptosporidium parvum | 20/20
(100%)
[83.2% - 100%] | 20/20
(100%)
[83.2% - 100%] | 100% |
| Cyclospora cayetanensis | Cyclospora cayetanensis | 20/20
(100%)
[83.2% - 100%] | 20/20
(100%)
[83.2% - 100%] | 100% |
| Entamoeba histolytica | Entamoeba histolytica | 11/20b
(55%)
[31.5% - 77.0%] | 15/20b
(75%)
[51.0% - 91.3%] | 80% |
| Giardia lamblia | Giardia intestinalis | 7/20b
(35%)
[15.4% - 59.2%] | 10/20b
(50%)
[27.2% - 72.8%] | 85% |
| | Viruses | | | |
| Adenovirus F 40/41 | Adenovirus F40 | 19/20
(95%)
[75.1% - 99.9%] | 20/20
(100%)
[83.2% - 100%] | 95% |
| | Adenovirus F41 | 20/20
(100%)
[83.2% - 100%] | 18/20a
(90%)
[68.3% - 98.8%] | 90% |
| Astrovirus | Astrovirus | 20/20
(100%)
[83.2% - 100%] | 20/20
(100%)
[83.2% - 100%] | 100% |
| Norovirus GI/GII | Norovirus GI | 18/20a
(90%)
[68.3% - 98.8%] | 19/20
(95%)
[75.1% - 99.9%] | 95% |
| Rotavirus A | Rotavirus A | 20/20
(100%)
[83.2% - 100%] | 20/20
(100%)
[83.2% - 100%] | 100% |
| Sapovirus | Sapovirus | 20/20
(100%)
[83.2% - 100%] | 20/20
(100%)
[83.2% - 100%] | 100% |

BioFire Diagnostics, LLC 510(k)
Multi-instrument FilmArray Gastrointestinal Panel

13

4 Initial testing of 20 replicates per system resulted in 20/20 Detected results on the current system and only 17/20 results on the modified system. Amplification data, which were comparable between the current and modified systems, indicated that the amount of analyte in the samples may have been below LoD, based on comparison to the original LoD study. Therefore, an additional 20 replicates were tested and the analyte was detected in 20/20 replicates (>95%) on both the current and modified systems. Data presented are the combination of the total number of replicates tested.

b Detection is lower than the expected 95% on the current and/or modified system(s) at LoD, though 95% confidence intervals are overlapping. Amplification data, which were comparable between the current and modified systems, indicated that the amount of analyte in the samples may have been below LoD, based on comparison to the original LoD study.

Tm values from the LoD replicate samples were compared to assess whether Tm data are equivalent between the current and modified FilmArray systems. Normal Tm variation of the current FilmArray system is ±0.5℃ and it was observed that mean Tm values for all FilmArray GI Panel assays on the modified system were ± 0.4℃ or less compared to the same samples tested on the current system (△Tm in Table 5).

Table 5. Comparison of Mean Tm Values for FilmArray GI Panel Analytes on the Current and Modified Systems

			Mean Tm Values		△Tm
GI Panel Test Result	Species/Isolate	Assay	Current
System	Modified
System	[Current-
Modified]
Bacteria
Campylobacter	Campylobacter jejuni	Campy1	77.8	77.9	-0.1
Clostridium difficile
Toxin A/B	Clostridium difficile	Cdiff Tm1	75.7	75.6	0.1
	Clostridium difficile	Cdiff Tm2	78.7	78.5	0.2
Plesiomonas shigelloides	Plesiomonas shigelloides	Pshig	90.7	90.4	0.3
Salmonella	Salmonella enterica
subsp. enterica	Salm	82.2	82.0	0.2
Vibrio/Vibrio cholerae	Vibrio cholerae	Vchol	81.5	81.7	-0.2
Vibrio	Vibrio parahaemolyticus	Vibrio	82.2	81.9	0.3
Yersinia enterocolitica	Yersinia enterocolitica	Yent	85.6	85.4	0.2
Diarrheagenic E. coli/Shigella
Enteroaggregative E. coli
(EAEC)	Escherichia coli (EAEC)	EAEC	79.1	79.0	0.1
Enteropathogenic E. coli
(EPEC)	Escherichia coli (EPEC)	Ec eae	80.6	80.4	0.2
Enterotoxigenic E. coli
(ETEC) It/st	Escherichia coli (ETEC)	ETEC1	80.7	80.5	0.2
	Escherichia coli (ETEC)	ETEC2	78.8	78.7	0.1
GI Panel Test Result	Species/Isolate	Assay	Mean Tm Values
Current System	Mean Tm Values
Modified System	△Tm
[Current-Modified]
		ETEC3	75.1	75.0	0.1
Shiga-like toxin-producing E.
coli (STEC) stx1/stx2	Escherichia coli (STEC)	STEC1	82.8	82.6	0.2
		STEC2	84.9	84.7	0.2
		EC O157	83.1	82.8	0.3
Shiga-like toxin-producing E.
coli (STEC) stx1/stx2
E. coli O157	Escherichia coli (STEC)
O157	STEC1	82.8	82.6	0.2
		STEC2	84.9	84.7	0.2
Shigella/Enteroinvasive
E. coli (EIEC)	Escherichia coli (EIEC)	Shig	86.3	86.4	-0.1
	Shigella sonnei	Shig	86.5	86.2	0.3
Parasites
Cryptosporidium	Cryptosporidium parvum	Crypt1	79.1	78.8	0.3
		Crypt2	71.8	71.7	0.1
Cyclospora cayetanensis	Cyclospora cayetanensis	Ccayet	86.6	86.3	0.3
Entamoeba histolytica	Entamoeba histolytica	Ehist	76.8	76.5	0.3
Giardia lamblia	Giardia lamblia	Glam	91.6	91.3	0.3
Viruses
Adenovirus F 40/41	Adenovirus F40	AdenoF	84.6	84.5	0.1
Adenovirus F 40/41	Adenovirus F41	AdenoF	86.8	86.5	0.3
Astrovirus	Astrovirus	Astro	85.5	85.3	0.2
Norovirus GI/GII	Norovirus GI	Noro1	83.6	83.8	-0.2
Rotavirus A	Rotavirus A	RotaA1
Tm1	78.3	77.9	0.4
	Rotavirus A	RotaA1
Tm2	81.2	80.8	0.4
		RotaA2	77.1	76.9	0.2
Sapovirus	Sapovius	Sapo	86.7	86.6	0.1

14

Reproducibility

15

A multicenter reproducibility study was performed to determine between-site/system and overall reproducibility of the FilmArray GI Panel on the multi-instrument FilmArray system.

Reproducibility testing occurred at three test sites using a panel of contrived stool samples, each spiked with various concentrations of five different GI Panel analytes. Each analyte was evaluated at three different concentrations (Negative, Low Positive and Moderate Positive).

The study incorporated a range of potential variation introduced by nine different operators, four different pouch lots, and nine different FilmArray 2.0instruments. A system consisted of three instruments connected to a single computer. Samples were stored refrigerated (4°C) and tested on four different days at three testing sites (one system, A, B, or C per site) for 108 data points per sample.

A summary of results (percent (%) agreement with the expected result) for each analyte (by site/system and overall) is provided in Table 6 alongside the overall % Agreement with Expected Results originally obtained on the single-instrument system.

| Organism
Tested | Concentration
Tested | Expected
Result | % Agreement with Expected Result
Multi-instrument
FilmArray System | | | Single-instrument
FilmArray System | |
|---------------------------------------------------------------------------|------------------------------------------------------------|--------------------------------------|--------------------------------------------------------------------------|------------------|------------------|---------------------------------------------------------|---------------------------------------------------------------------------------------|
| | | | Site/System
A | Site/System
B | Site/System
C | All Sites/Systems
(95% Confidence
Interval) | All Sites
(95% Confidence
Interval) |
| Clostridium
difficile
(toxinotype 0
A+B+) ATCC
9689 | Moderate
Positive
3x LoD
$1.2x10^6$
CFU/mL | Detected | 36/36
100% | 36/36
100% | 36/36
100% | 108/108
100%
(96.6-100%) | 108/108
100%
(96.6 - 100%) |
| | Low Positive
1x LoD
$4.0x10^5$
CFU/mL | Detected | 35/36
97.2% | 36/36
100% | 36/36
100% | 107/108
99.1%
(95.0-100%) | 108/108
100%
(96.6 - 100%) |
| | Negative | Not
Detected | 36/36
100% | 36/36
100% | 36/36
100% | 108/108
100%
(96.6-100%) | 360/360
100%
(96.6 - 100%) |
| Shiga-toxin
producing
Escherichia coli
(STEC O157)
ATCC 43895 | Moderate
Positive
3x LoD
$3.0x10^4$
CFU/mL | Detected | 36/36
100% | 36/36
100% | 36/36
100% | 108/108
100%
(96.6-100%) | 90/90
100%
(96.0 - 100%) |
| | Low Positive
1x LoD
$1.0x10^4$
CFU/mL | Detected | 36/36
100% | 36/36
100% | 36/36
100% | 108/108
100%
(96.6-100%) | 90/90
100%
(96.0 - 100%) |
| | Negative | Not
Detected
and N/A
(O157) | 36/36
100% | 36/36
100% | 36/36
100% | 108/108
100%
(96.6-100%) | 576/576
100%
(99.4 - 100%) |
| Organism
Tested | Concentration
Tested | Expected
Result | Multi-instrument
FilmArray System | | | All
Sites/Systems
(95%
Confidence
Interval) | Single-instrument
FilmArray System
All Sites
(95%
Confidence
Interval) |
| | | | Site/System
A | Site/System
B | Site/System
C | | |
| Cryptosporidium
parvum
Waterborne
P102C | Moderate
Positive
3x LoD
$1.5x10^4$
oocysts/mL | Detected | 36/36
100% | 36/36
100% | 36/36
100% | 108/108
100%
(96.6-100%) | 90/90
100%
(96.0 - 100%) |
| | Low Positive
1x LoD
$5.0x10^3$
oocysts/mL | Detected | 35/36
97.2% | 36/36
100% | 36/36
100% | 107/108
99.1%
(95.0-100%) | 90/90
100%
(96.0 - 100%) |
| | Negative | Not
Detected | 36/36
100% | 36/36
100% | 36/36
100% | 108/108
100%
(96.6-100%) | 576/576
100%
(99.4 - 100%) |
| Adenovirus F41
ATCC VR-930 | Moderate
Positive
3x LoD
300 TCID50/mL | Detected | 36/36
100% | 36/36
100% | 36/36
100% | 108/108
100%
(96.6-100%) | 90/90
100%
(96.0 - 100%) |
| | Low Positive
1x LoD
100 TCID50/mL | Detected | 36/36
100% | 36/36
100% | 36/36
100% | 108/108
100%
(96.6-100%) | 90/90
100%
(96.0 - 100%) |
| | Negative | Not
Detected | 36/36
100% | 36/36
100% | 36/36
100% | 108/108
100%
(96.6-100%) | 576/576
100%
(99.4 - 100%) |
| Astrovirus
NCPV
10037071v | Moderate
Positive
3x LoD
150 FFU/mL | Detected | 36/36
100% | 36/36
100% | 36/36
100% | 108/108
100%
(96.6-100%) | 90/90
100%
(96.0 - 100%) |
| | Low Positive
1x LoD
50 FFU/mL | Detected | 36/36
100% | 36/36
100% | 36/36
100% | 108/108
100%
(96.6-100%) | 90/90
100%
(96.0 - 100%) |
| | Negative | Not
Detected | 36/36
100% | 36/36
100% | 36/36
100% | 108/108
100%
(96.6-100%) | 576/576
100%
(99.4 - 100%) |

Table 6. Reproducibility of the FilmArray GI Panel Test Results

16

ª Summary of Reproducibility study results for select analytes taken from the original Reproducibility evaluation performed on the single-instrument FilmArray system (SDY-011541 "Evaluation of Reproducibility for the FilmArray Gastrointestinal (GI) Panel'').

The test results obtained for the Gastrointestinal Panel on the FilmArray 2.0 were highly reproducible and are consistent with the data collected on the currentFilmArray in the original GI Panel Reproducibility evaluation.

The reproducibility of Tm for each positive assay was also evaluated by site/system and overall (all sites/systems) and a summary is provided in Table 7.

17

					Tm Reproducibility
Organism	Assay		Test Level	Test Site	Mean	StDev Tm
			Bacteria and (Including Diarrheagenic E. coli)
			Moderate Positive
3x LoD
1.2x106 cells/mL	Site A	75.5	± 0.2
				Site B	75.3	± 0.4
				Site C	75.0	± 0.4
Clostridium difficile
ATCC 9689	Cdiff			All Sites	75.3	± 0.4
				Low Positive
1x LoD
4x105 cells/mL	Site A	76.2
					Site B	76.0
					Site C	75.7
			All Sites		76.0	± 0.6
		Tm 2	Moderate Positive
3x LoD
1.2x106 cells/mL	Site A	78.7	± 0.2
				Site B	78.6	±0.3
				Site C	78.3	±0.3
				All Sites	78.5	± 0.4
			Low Positive
1x LoD
4x105 cells/mL	Site A	79.1	± 0.3
				Site B	78.9	± 0.4
				Site C	78.6	± 0.4
				All Sites	78.9	± 0.4
	O157		Moderate Positive
3x LoD
3x104 CFU/mL	Site A	83.6	±0.2
				Site B	83.4	±0.3
				Site C	83.1	±0.3
				All Sites	83.4	±0.3
Escherichia coli
(STEC) O157
ATCC 43895			Low Positive
1x LoD
1x104 CFU/mL	Site A	83.5	±0.2
				Site B	83.4	±0.2
				Site C	83.0	±0.3
				All Sites	83.3	±0.3
	STEC 1		Moderate Positive
3x LoD
3x104 CFU/mL	Site A	83.2	±0.1
				Site B	83.0	±0.3
				Site C	82.7	±0.3
				All Sites	83.0	±0.3
			Low Positive
1x LoD
1x104 CFU/mL	Site A	83.1	±0.2
				Site B	83.0	±0.2
				Site C	82.7	±0.3
				All Sites	83.0	±0.3
	STEC 2		Moderate Positive
3x LoD
3x104 CFU/mL	Site A	85.4	±0.2
				Site B	85.2	±0.2
				Site C	84.9	±0.3
				All Sites	85.1	±0.3
			Low Positive
1x LoD
1x104 CFU/mL	Site A	85.3	±0.2
				Site B	85.2	±0.2
				Site C	84.9	±0.3
				All Sites	85.1	±0.3
			Protozoa
Cryptosporidium
parvum Waterborne
P102C	Crypt 1		Moderate Positive
3x LoD
1.5x104 oocysts/mL	Site A	79.5	±0.2
				Site B	79.4	±0.3
				Site C	79.0	±0.3
				All Sites	79.3	±0.3
			Low Positive
1x LoD	Site A	79.6	±0.2
				Site B	79.5	±0.3
				Tm Reproducibility
Organism	Assay	Test Level	Test Site	Mean	StDev Tm
		5x103 oocysts/mL	Site C	79.2	+0.3
			All Sites	79.5	+0.3
	Crypt 2	Moderate Positive
3× LoD
1.5x104 oocysts/mL	Site A	71.8	±0.2
			Site B	71.7	+0.3
			Site C	71.4	+0.3
			All Sites	71.6	+0.3
		Low Positive
1× LoD
5x103 oocysts/mL	Site A	72.2	+0.3
			Site B	72.1	+0.4
			Site C	72.0	+0.4
			All Sites	72.1	+0.4
Viruses
Adenovirus F41
ATTC VR-930	AdenoF	Moderate Positive
3× LoD
300 TCID50/mL	Site A	86.9	+0.2
			Site B	86.8	+0.3
			Site C	86.4	+0.3
			All Sites	86.7	+0.4
		Low Positive
1× LoD
100 TCID50/mL	Site A	87.1	±0.2
			Site B	86.9	+0.3
			Site C	86.6	+0.3
			All Sites	86.8	+0.3
Astrovirus
(Type 8)
NCPV 1003071v	Astro	Moderate Positive
3× LoD
150 FFU/mL	Site A	85.9	+0.1
			Site B	85.8	+0.2
			Site C	85.4	+0.3
			All Sites	85.7	+0.3
		Low Positive
1× LoD
50 FFU/mL	Site A	86.0	±0.2
			Site B	85.8	+0.2
			Site C	85.5	+0.3
			All Sites	85.7	+0.3

Table 7. Reproducibility of Tm for Positive FilmArray GI Panel Assays on Multi-instrument FilmArray 2.0 Systems

18

4 A characteristic double melt profile is observed when both C. difficile toxin genes (tcdA and tcdB) are present in a sample and two different Tm values are reported (Tm1 and Tm2).