K Number

Device Name

Accelerate Pheno System, Accelerate PhenoTest BC Kit

Manufacturer

Accelerate Diagnostics, Inc.

Date Cleared

2020-09-15

(356 days)

Product Code

PRH LON NSU PAM PEN PEO

Regulation Number

866.1650

Intended Use

The Accelerate PhenoTest™ BC kit is a multiplexed in vitro diagnostic test utilizing both qualitative nucleic acid fluorescence in situ hybridization (FISH) identification and quantitative, antimicrobial susceptibility testing (AST) methods and is intended for use with the Accelerate Pheno™ system. The Accelerate PhenoTest™ BC kit is capable of simultaneous detection and identification of multiple microbial targets followed by susceptibility testing of the appropriate detected bacterial organisms. The Accelerate PhenoTest™ BC kit is performed directly on blood culture samples identified as positive by a continuous monitoring blood culture system. Results are intended to be interpreted in conjunction with Gram stain results. The Accelerate PhenoTest™ BC kit identifies the following Gram-positive and Gram-negative bacteria and yeasts utilizing FISH probes targeting organism-specific ribosomal RNA sequences: Staphylococcus aureus, Staphylococcus lugdunensis, Coagulase-negative Staphylococcus species (i.e., Staphylococcus epidermidis, Staphylococcus haemolyticus, Staphylococcus capits, Staphylococcus lugdunensis, Staphylococcus warneri, not differentiated), Enterococcus faecum, Streptococus spp. (i.e., Streptococus mitis, Streptococcus oralis, Streptococcus gallolyticus, Streptococcus agalactiae, Streptococus pneumoniae, not differentiated), Pseudomonas aeruginosa, Acinetobacter baumannii, Klebsiella pneumoniae, Klebsiella oxytoca, not differentiated), Escherichia coli, Enterobacter cloacae, Enterobacter (Klebsiella) aerogenes, not differentiated), Proteus mirabilis, Proteus vulgaris, not differentiated), Citrobacter spp. (i.e., Citrobacter koseri, not differentiated), Serratia marcescens, Candida albicans and Candida glabrata. The Accelerate PhenoTest™ BC kit tests the following antimicrobial agents with the specific target organisms identified below: Amikacin: Pseudomonas aeruginosa, Acinetobacter baumannii, Klebsiella pneumoniae, Klebsiella oxytoca, not differentiated), Escherichia coli, Enterobacter cloacae, Enterobacter (Klebsiella) aerogenes, not differentiated), Proteus mirabilis, Proteus vulgaris, not differentiated), Citrobacter spp. (i.e., Citrobacter freundii, Citrobacter koseri, not differentiated) and Serratia marcescens Ampicillin: Enterococcus faecalis and Enterococcus faecium Ampicillin/Sulbactam: Escherichia coli, Klebsiella spp. (i.e., Klebsiella pneumoniae, Klebsiella oxytoca, not differentiated), and Proteus spp. (i.e., Proteus mirabilis, Proteus vulgaris, not differentiated) Aztreonam: Pseudomonas aeruginosa, Klebsiella spp. (i.e., Klebsiella pneumoniae, Klebsiella oxytoca, not differentiated), Escherichia coli, Enterobacter spp. (i.e., Enterobacter (Klebsiella) aerogenes, not differentiated), Proteus spp. (i.e., Proteus mirabilis, Proteus vulgaris, not differentiated), Citrobacter freundii, Citrobacter koseri, not differentiated) and Serratia marcescens Ceftazidime: Pseudomonas aeruginosa, Klebsiella pneumoniae, Klebsiella pneumoniae, Klebsiella oxytoca, not differentiated), Escherichia coli, Enterobacter spp. (i.e., Enterobacter (Klebsiella) aerogenes, not differentiated), Proteus spp. (i.e., Proteus vulgaris, not differentiated), Citrobacter spp. (i.e., Citrobacter freundii, Citrobacter koseri, not differentiated) and Serratia marcescens Ceftaroline: Staphylococcus aureus Cefepime: Pseudomonas aeruginosa, Klebsiella pneumoniae, Klebsiella oxytoca, not differentiated), Escherichia coli, Enterobacter spp. (i.e., Enterobacter (Klebsiella) aerogenes, not differentiated), Proteus spp. (i.e., Proteus mirabilis, Proteus vulgaris, not differentiated), Citrobacter freundii, Citrobacter koseri, not differentiated) and Serratia marcescens Ceftriaxone: Klebsiella spp. (i.e., Klebsiella pneumoniae, Klebsiella oxytoca, not differentiated), Escherichia coli, Enterobacter spp. (i.e., Enterobacter (Klebsiella) aerogenes, not differentiated), Proteus spp. (i.e., Proteus mirabilis, Proteus vulgaris, not differentiated), Citrobacter freundii, Citrobacter koseri, not differentiated) and Serratia marcescens Ciprofloxacin: Pseudomonas aeruginosa, Klebsiella spp. (i.e., Klebsiella pneumoniae, Klebsiella oxytoca, not differentiated), Escherichia coli, Enterobacter spp. (i.e., Enterobacter (Klebsiella) aerogenes, not differentiated), Proteus spp. (i.e., Proteus vulgaris, not differentiated), Citrobacter spp. (i.2., Citrobacter freundii, Citrobacter koseri, not differentiated) and Serratia marcescens Daptomycin: Staphylococcus aureus, Coagulase-negative Staphylococcus species (i.e., Staphylococcus epidermidis, Staphylococcus haemolyticus, Staphylococcus hominis, Staphylococcus capitis, Staphylococcus lugdunensis, Staphylococcus warneri, not differentiated), Enterococcus faecalis and Enterococcus faecium Ertapenem: Klebsiella spp. (i.e., Klebsiella pneumoniae, Klebsiella oxytoca, not differentiated), Escherichia coli, Enterobacter spp. (i.e., Enterobacter (Klebsiella) aerogenes, not differentiated), Proteus spp. (i.e., Proteus mirabilis, Proteus vulgaris, not differentiated), Citrobacter freundii, Citrobacter koseri, not differentiated) and Serratia marcescens Gentamicin: Pseudomonas aeruginosa, Klebsiella spp. (i.e., Klebsiella pneumoniae, Klebsiella oxytoca, not differentiated), Escherichia coli, Enterobacter spp. (i.e., Enterobacter (Klebsiella) aerogenes, not differentiated), Proteus spp. (i.e., Proteus vulgaris, not differentiated), Citrobacter spp. (i.e., Citrobacter freundii, Citrobacter koseri, not differentiated) and Serratia marcescens Linezolid: Staphylococcus aureus, Enterococcus faecalis and Enterococcus faecium Meropenem: Pseudomonas aeruginosa, Klebsiella spp. (i.e., Klebsiella pneumoniae, Klebsiella oxytoca, not differentiated), Escherichia coli, Enterobacter spp. (i.e., Enterobacter (Klebsiella) aerogenes, not differentiated), Proteus spp. (i.e., Proteus vulgaris, not differentiated), Citrobacter spp. (i.e., Citrobacter freundii, Citrobacter koseri, not differentiated) and Serratia marcescens Piperacillin/Tazobactam: Pseudomonas aeruginosa, Acinetobacter baumannii, Klebsiella pneumoniae, Klebsiella oxytoca, not differentiated), Escherichia coli, Enterobacter cloacae, Enterobacter (Klebsiella) aerogenes, not differentiated), Proteus mirabilis, Proteus vulgaris, not differentiated), Citrobacter spp. (i.e., Citrobacter koseri, not differentiated) and Seratia marcescens Tobramycin: Pseudomonas aeruginosa, Klebsiella spp. (i.e., Klebsiella pneumoniae, Klebsiella oxytoca, not differentiated), Escherichia coli, Enterobacter spp. (i.e., Enterobacter (Klebsiella) aerogenes, not differentiated), Proteus spp. (i.e., Proteus vulgaris, not differentiated), Citrobacter spp. (i.e., Citrobacter freundii, Citrobacter koseri, not differentiated) and Serratia marcescens Vancomycin: Staphylococcus aureus. Staphylococcus lugdunensis. Coagulase- negative Staphylococcus species (i.e., Staphylococcus epidermidis, Staphylococcus haemolyticus, Staphylococus hominis, Staphylococcus capitis, Staphylococus lugdunensis, Staphylococus warneri, not differentiated), Enterococcus faecius and Enterococus faccium The following resistance phenotype is reported based on qualitative tests: Methicillin-resistance (S. aureus S. Jugdunensis, coagulase negative staphylococci). The Accelerate PhenoTest™ BC kit is indicated as an aid in the diagnosis of bacteremia and fungemia. It is also indicated for susceptibility testing of specific pathogenic bacteria as identified above commonly associated with or causing bacteremia. Results are intended to be used in conjunction with other clinical and laboratory findings. Standard laboratory protocols for processing positive blood cultures should be followed to ensure availability of isolates for supplemental testing as needed. Additionally, subculture of positive blood culture is necessary for the identification and susceptibility testing of: organisms not identified by the Accelerate PhenoTest™ BC kit, organisms present in polymicrobial samples, organisms for which species identification is critical for patient care (e.g. speciation of Streptococus spp.), samples for which an "indeterminate" result for any probe was obtained, for testing antimicrobial agents not included on the Accelerate panel and for epidemiologic testing.

Device Description

The Accelerate PhenoTest™ BC kit contains a sample vial, a 48-channel disposable test cassette and a reagent cartridge. All identification (ID) and antimicrobial susceptibility testing (AST) is performed in individual flowcells of the test cassette. The reagent cartridge contains gel electrofiltration (GEF) stations, fluorescence in situ hybridization (FISH) probes, antimicrobials, and reagents for automated sample preparation, identification of bacterial and fungal target organisms, and antimicrobial susceptibility and resistance marker detection testing for bacterial target organisms. The user loads the sample into the sample vial, places the test cassette, reagent cartridge and sample vial into an Accelerate Pheno™ system module, then presses the module button to close the module door and start the run. The rest of the operations are automated as described below. Automated sample preparation is performed using gel electrofiltration (GEF) which is based on gel electrophoresis principles. Sample is automatically transferred to a gel well containing pores smaller than bacterial or yeast cells. Application of an electric field causes lysed blood cells and/or other sample debris to pass into the gel wall while bacterial/yeast cells remain inside the gel well. The electric field is briefly reversed to dislodge bacterial/yeast cells from the gel wall prior to removal. Following sample preparation, recovered cells are automatically pipetted into multiple flowcell channels of the test cassette. Conductive layers of transparent indium tin oxide (TTO) coat the top and bottom inner surfaces of each flowcell channel and act as electrodes. An additional cationic poly-L-lysine layer on the bottom of each flowcell acts as a capture surface. When a voltage is applied, the negatively-charged bacterial/yeast cells migrate to the positively-charged capture surface where they are captured prior to imaging. Cocktails of ATTO-532 (green) fluorescently-labeled DNA probes bind to the ribosomal RNA of target organisms following permeabilization. Each cocktail also includes ATTO-647 (red) labeled universal bacterial probe that binds to the ribosomal RNA of all clinically relevant bacteria (bacterial ID channels) or universal eukaryotic probe that binds to the ribosomal RNA of all clinically relevant yeast (yeast ID channels). The system images each flowcell using a fluorescence and dark-field microscope with camera and a filter set that captures emission from the FISH ID probes at 532 nm. 647 nm and in dark-field. An additional filter, capturing emission at 720 nm, is utilized prior to FISH ID for removal of interfering sample debris. To further exclude debris, only dark-field objects colocalized with universal probe signal are included in analysis. Colocalization of target probe signal and universal probe signal identifies a target organism. The software also quantitates the total number of organisms present in a sample using a nucleic acid stain in a separate control flowcell. Comparing the relative numbers of each target organism to the number of objects lit up by the universal probes allows the system to differentiate bacteria/yeast from debris. FISH ID results are reported approximately 2 hours after loading the sample, and the ID result determines the selection of appropriate antimicrobials for subsequent antimicrobial susceptibility testing. The Accelerate Pheno™ system leverages Morphokinetic Cellular Analysis (MCA) technology to measure distinct morphokinetic features of live microbial cells responding to antimicrobials to generate susceptibility results. MCA is a computer vision based analytical method that uses digital microscopy inputs and machine learning technology to observe individual live cells and microcolonies (or clones) and recognize patterns of change over time. This technology tracks and analyzes multiple morphological and kinetic changes of individual cells and microcolonies under a variety of conditions. These changes include morphokinetic features such as cell morphology, mass as measured by light intensity of a growing microcolony, division rate, anomalous growth patterns, and heterogeneity. Prior to AST, the remaining sample is combined with growth media and undergoes a pregrowth step during the FISH ID assay to normalize growth rates. Following automated sample preparation, the cells are quantitated and dynamically diluted to the appropriate concentration for AST testing. The cells are then captured in flowcell channels and immobilized when growth media containing single concentrations of each test antimicrobial are added to separate flowcell channels. The bacteria in each flowcell are imaged every 10 minutes for up to 4.5 hours, creating a time-lapse record of bacterial growth from individual progenitor cells into clones of daughter cells. During this period, morphokinetic features are measured and used for analysis. The precise quantitative measurement of individual clone growth rate over time is a powerful indicator of antimicrobial efficacy. Onboard software algorithms derive minimum inhibitory concentration (MIC) values from the measured features, and apply appropriate expert rules for proper interpretation and reporting of categorical interpretations - S, I or R (susceptible, intermediate, or resistant). The Accelerate Pheno™ system is designed to perform Accelerate PhenoTest™ BC kit identification (ID) of bacterial and yeast cells and antimicrobial susceptibility testing (AST) in approximately 7 hours directly from positive blood culture samples. Depending on the computer configuration, up to eight ID/AST modules can be operated concurrently. Analysis time may increase when four or more tests are performed on ID/AST modules simultaneously. Other factors, such as samplexity, the number of organisms and/or antimicrobials available in the panel, may also increase time to result. The Accelerate PhenoTest™ BC ID and AST OC tests automate the external QC testing procedure, removing the manual standardized inoculum preparation and manual dispensing of the McFarland standardized inoculum (0.5 for bacteria and 2.0 for fungi). This reduces the complexity of QC testing, eliminating the need for a clinical scientist to perform the test. Furthermore, the stability of the analyte is increased through the use of complementary sequences coupled to polymer microspheres for each of the target probes in the Accelerate PhenoTest™ BC kit. As accessories to the Accelerate PhenoTest™ BC kit and Accelerate Pheno™ system, the Accelerate PhenoTest™ BC ID and AST QC tests have their own instructions for use. The Accelerate Pheno™ system is a fully-integrated in vitro diagnostic system comprised of one to eight ID/AST module(s), a computing system, touchscreen monitor and Accelerate Pheno™ system software for use with Accelerate PhenoTest™ kits. It is designed to perform identification (ID) of bacterial and yeast cells and antimicrobial susceptibility testing (AST) in approximately 7 hours directly from positive blood culture samples. Depending on the computer configuration, up to eight ID/AST modules can be operated concurrently. Analysis time may increase when four or more tests are initiated on ID/AST modules simultaneously. Other factors, such as sample complexity, the number of organisms and/or antimicrobials available in the assay kit panel, may also increase time to result. Identification uses fluorescence in situ hybridization (FISH) and susceptibility testing uses microscopic observation of individual, live, growing bacterial cells in near real time (approximately every 10 minutes) in the presence of antimicrobial agents. The Accelerate Pheno™ system is comprised of the following hardware: - Accelerate Pheno™ system ID/AST modules (Up to 4 or 8 depending on . computing system architecture) - Computing system, either: ● - Control PC/Analysis PC setup (supports up to 4 ID/AST modules): o - ▪ - 1 Analysis PC - Interface PC/Analysis module setup (supports up to 8 ID/AST modules): o - 1 Interface PC . - . 1 Analysis module - Touchscreen monitor ● - Keyboard ● - Mouse ● - Power cords ● - . Cables - Uninterruptible Power Supply (1 UPS for up to 4 ID/AST modules and 1 UPS per ● computing system) Each system contains up to 4 or 8 ID/AST modules (depending on computing system) and each ID/AST module can run one patient sample at a time. Each ID/AST module may be started or stopped at any time, independent of the other ID/AST modules.

More Information

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Center

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DEN160032

Reference Devices

Not Found

AI/ML (Artificial Intelligence / Machine Learning)

Yes
The device description explicitly states that the Accelerate Pheno™ system leverages "machine learning technology" as part of its Morphokinetic Cellular Analysis (MCA) technology.

Therapeutic

No
This device is an in vitro diagnostic test that identifies microbial targets and determines their antimicrobial susceptibility. It provides information for diagnosis and treatment decisions, but it does not directly treat a disease or condition.

Diagnostic

Yes.

The device is an "in vitro diagnostic test" intended for "simultaneous detection and identification of multiple microbial targets followed by susceptibility testing" and is indicated as an "aid in the diagnosis of bacteremia and fungemia".

SaMD (Software as a Medical Device)

The device description explicitly states that the Accelerate Pheno™ system is a "fully-integrated in vitro diagnostic system comprised of one to eight ID/AST module(s), a computing system, touchscreen monitor and Accelerate Pheno™ system software". It also lists several hardware components including ID/AST modules, computing systems (PCs and analysis modules), a touchscreen monitor, keyboard, mouse, power cords, cables, and an Uninterruptible Power Supply. While software is a critical component, the device relies on significant hardware for its function.

IVD (In Vitro Diagnostic)

Yes, this device is an IVD (In Vitro Diagnostic).

Here's why:

Explicitly Stated Intended Use: The document clearly states in the "Intended Use / Indications for Use" section: "The Accelerate PhenoTest™ BC kit is a multiplexed in vitro diagnostic test..." and "The Accelerate Pheno™ system is a fully-integrated in vitro diagnostic system...".
Testing Performed on Biological Samples: The device is intended for use with "blood culture samples identified as positive by a continuous monitoring blood culture system." This involves testing biological material taken from the human body.
Provides Diagnostic Information: The device performs identification of microorganisms and antimicrobial susceptibility testing, which are crucial for aiding in the diagnosis of bacteremia and fungemia and guiding treatment decisions.
Used in a Laboratory Setting: The description mentions "Standard laboratory protocols for processing positive blood cultures should be followed" and the device is described as a "system" with components like a computing system, monitor, and modules, indicating use in a clinical laboratory or similar setting.

PCCP (Predetermined Change Control Plan) Authorized

No
The provided text does not contain any explicit statement that the FDA has reviewed and approved or cleared a Predetermined Change Control Plan (PCCP) for this specific device.

Overview

Intended Use / Indications for Use

The Accelerate PhenoTest™ BC kit identifies the following Gram-positive and Gramnegative bacteria and yeasts utilizing FISH probes targeting organism-specific ribosomal RNA sequences:

Staphylococcus aureus, Staphylococcus lugdunensis, Coagulase-negative Staphylococcus species (i.e., Staphylococcus epidermidis, Staphylococcus haemolyticus, Staphylococcus hominis, Staphylococcus capitis, Staphylococcus lugdunensis, Staphylococcus warneri, not differentiated), Enterococcus faecalis, Enterococcus faecium, Streptococcus spp. (i.e., Streptococcus mitis, Streptococcus oralis, Streptococcus gallolyticus, Streptococcus agalactiae, Streptococcus pneumoniae, not differentiated), Pseudomonas aeruginosa, Acinetobacter baumannii, Klebsiella spp. (i.e., Klebsiella pneumoniae, Klebsiella oxytoca, not differentiated), Escherichia coli, Enterobacter spp. (i.e., Enterobacter cloacae, Enterobacter (Klebsiella) aerogenes, not differentiated), Proteus spp. (i.e., Proteus mirabilis, Proteus vulgaris, not differentiated), Citrobacter spp. (i.e., Citrobacter freundii, Citrobacter koseri, not differentiated), Serratia marcescens, Candida albicans and Candida glabrata.

The Accelerate PhenoTest™ BC kit tests the following antimicrobial agents with the specific target organisms identified below:

Amikacin: Pseudomonas aeruginosa, Acinetobacter baumannii, Klebsiella spp. (i.e., Klebsiella pneumoniae, Klebsiella oxytoca, not differentiated), Escherichia coli, Enterobacter spp. (i.e., Enterobacter cloacae, Enterobacter (Klebsiella) aerogenes, not differentiated), Proteus spp. (i.e., Proteus mirabilis, Proteus vulgaris, not differentiated), Citrobacter spp. (i.e., Citrobacter freundii, Citrobacter koseri, not differentiated) and Serratia marcescens

Ampicillin: Enterococcus faecalis and Enterococcus faecium

Ampicillin/Sulbactam: Escherichia coli, Klebsiella spp. (i.e., Klebsiella pneumoniae, Klebsiella oxytoca, not differentiated), and Proteus spp. (i.e., Proteus mirabilis, Proteus vulgaris, not differentiated)

Aztreonam: Pseudomonas aeruginosa, Klebsiella spp. (i.e., Klebsiella pneumoniae, Klebsiella oxytoca, not differentiated), Escherichia coli, Enterobacter spp. (i.e., Enterobacter cloacae. Enterobacter (Klebsiella) aerogenes, not differentiated), Proteus spp. (i.e., Proteus mirabilis, Proteus vulgaris, not differentiated), Citrobacter spp. (i.e., Citrobacter freundii, Citrobacter koseri, not differentiated) and Serratia marcescens

Ceftazidime: Pseudomonas aeruginosa, Klebsiella spp. (i.e., Klebsiella pneumoniae, Klebsiella oxytoca, not differentiated), Escherichia coli, Enterobacter spp. (i.e., Enterobacter cloacae, Enterobacter (Klebsiella) aerogenes, not differentiated), Proteus spp. (i.e., Proteus mirabilis, Proteus vulgaris, not differentiated), Citrobacter spp. (i.e., Citrobacter freundii, Citrobacter koseri, not differentiated) and Serratia marcescens

Ceftaroline: Staphylococcus aureus

Cefepime: Pseudomonas aeruginosa, Klebsiella spp. (i.e., Klebsiella pneumoniae, Klebsiella oxytoca, not differentiated), Escherichia coli, Enterobacter spp. (i.e., Enterobacter cloacae, Enterobacter (Klebsiella) aerogenes, not differentiated), Proteus spp. (i.e., Proteus mirabilis, Proteus vulgaris, not differentiated), Citrobacter spp. (i.e., Citrobacter freundii, Citrobacter koseri, not differentiated) and Serratia marcescens

Ceftriaxone: Klebsiella spp. (i.e., Klebsiella pneumoniae, Klebsiella oxytoca, not differentiated), Escherichia coli, Enterobacter spp. (i.e., Enterobacter cloacae, Enterobacter (Klebsiella) aerogenes, not differentiated), Proteus spp. (i.e., Proteus mirabilis, Proteus vulgaris, not differentiated), Citrobacter spp. (i.e., Citrobacter freundii, Citrobacter koseri, not differentiated) and Serratia marcescens

Ciprofloxacin: Pseudomonas aeruginosa, Klebsiella spp. (i.e., Klebsiella pneumoniae, Klebsiella oxytoca, not differentiated), Escherichia coli, Enterobacter spp. (i.e., Enterobacter cloacae. Enterobacter (Klebsiella) aerogenes, not differentiated), Proteus spp. (i.e., Proteus mirabilis, Proteus vulgaris, not differentiated), Citrobacter spp. (i.e., Citrobacter freundii, Citrobacter koseri, not differentiated) and Serratia marcescens

Daptomycin: Staphylococcus aureus, Coagulase-negative Staphylococcus species (i.e., Staphylococcus epidermidis, Staphylococcus haemolyticus, Staphylococcus hominis, Staphylococcus capitis, Staphylococcus lugdunensis, Staphylococcus warneri, not differentiated), Enterococcus faecalis and Enterococcus faecium

Ertapenem: Klebsiella spp. (i.e., Klebsiella pneumoniae, Klebsiella oxytoca, not differentiated), Escherichia coli, Enterobacter spp. (i.e., Enterobacter cloacae, Enterobacter (Klebsiella) aerogenes, not differentiated), Proteus spp. (i.e., Proteus mirabilis, Proteus vulgaris, not differentiated), Citrobacter spp. (i.e., Citrobacter freundii, Citrobacter koseri, not differentiated) and Serratia marcescens

Gentamicin: Pseudomonas aeruginosa, Klebsiella spp. (i.e., Klebsiella pneumoniae, Klebsiella oxytoca, not differentiated), Escherichia coli, Enterobacter spp. (i.e., Enterobacter cloacae. Enterobacter (Klebsiella) aerogenes, not differentiated), Proteus spp. (i.e., Proteus mirabilis, Proteus vulgaris, not differentiated), Citrobacter spp. (i.e., Citrobacter freundii, Citrobacter koseri, not differentiated) and Serratia marcescens

Linezolid: Staphylococcus aureus, Enterococcus faecalis and Enterococcus faecium

Meropenem: Pseudomonas aeruginosa, Klebsiella spp. (i.e., Klebsiella pneumoniae, Klebsiella oxytoca, not differentiated), Escherichia coli, Enterobacter spp. (i.e., Enterobacter cloacae, Enterobacter (Klebsiella) aerogenes, not differentiated), Proteus spp. (i.e., Proteus mirabilis, Proteus vulgaris, not differentiated), Citrobacter spp. (i.e., Citrobacter freundii, Citrobacter koseri, not differentiated) and Serratia marcescens

Piperacillin/Tazobactam: Pseudomonas aeruginosa, Acinetobacter baumannii, Klebsiella spp. (i.e., Klebsiella pneumoniae, Klebsiella oxytoca, not differentiated), Escherichia coli, Enterobacter spp. (i.e., Enterobacter cloacae, Enterobacter (Klebsiella) aerogenes, not differentiated), Proteus spp. (i.e., Proteus mirabilis, Proteus vulgaris, not differentiated), Citrobacter spp. (i.e., Citrobacter freundii, Citrobacter koseri, not differentiated) and Serratia marcescens

Tobramycin: Pseudomonas aeruginosa, Klebsiella spp. (i.e., Klebsiella pneumoniae, Klebsiella oxytoca, not differentiated), Escherichia coli, Enterobacter spp. (i.e., Enterobacter cloacae, Enterobacter (Klebsiella) aerogenes, not differentiated), Proteus spp. (i.e., Proteus mirabilis, Proteus vulgaris, not differentiated), Citrobacter spp. (i.e., Citrobacter freundii, Citrobacter koseri, not differentiated) and Serratia marcescens

Vancomycin: Staphylococcus aureus, Staphylococcus lugdunensis, Coagulase-negative Staphylococcus species (i.e., Staphylococcus epidermidis, Staphylococcus haemolyticus, Staphylococcus hominis, Staphylococcus capitis, Staphylococcus lugdunensis, Staphylococcus warneri, not differentiated), Enterococcus faecalis and Enterococcus faecium

The following resistance phenotype is reported based on a qualitative test: Methicillinresistance (S. aureus S. lugdunensis, coagulase negative staphylococci).

The Accelerate PhenoTest™ BC kit is indicated as an aid in the diagnosis of bacteremia and fungemia. It is also indicated for susceptibility testing of specific pathogenic bacteria as identified above commonly associated with or causing bacteremia. Results are intended to be used in conjunction with other clinical and laboratory findings.

Standard laboratory protocols for processing positive blood cultures should be followed to ensure availability of isolates for supplemental testing as needed. Additionally, subculture of positive blood culture is necessary for the identification and susceptibility testing of: organisms not identified by the Accelerate PhenoTest™ BC kit, organisms present in polymicrobial samples, organisms for which species identification is critical for patient care (e.g. speciation of Streptococcus spp.), samples for which an "indeterminate" result for any probe was obtained, for testing antimicrobial agents not included on the Accelerate panel and for epidemiologic testing.

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

PRH, NSU, PEO, PAM, PEN, LON

Device Description

Mentions image processing

Yes

Mentions AI, DNN, or ML

Input Imaging Modality

Fluorescence and dark-field microscopy.

Anatomical Site

Not Found

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

Performance of the modified Accelerate PhenoTest™ BC kit aztreonam (ATM), ceftazidime (CAZ), cefepime (FEP), meropenem (MEM) and piperacillin-tazobactam (TZP) Pseudomonas aeruginosa assays was established during an internal performance evaluation study at Accelerate Diagnostics, Inc. A total of 131 characterized Pseudomonas aeruginosa isolates were tested at the internal site in two phases along with evaluation of the new algorithms on the original 13 clinical trial isolates for a total of 144 isolates included in the performance evaluation. Phase 1 included testing of 100 challenge and stock isolates (115 total runs), and Phase 2 evaluated an additional 31 onscale isolates. P. aeruginosa isolates were seeded into BD BACTEC™ Plus Aerobic blood culture bottles containing healthy donor blood and incubated until positivity on the BD BACTECTM system. Samples from positive blood culture bottles were Gramstained, run on the Accelerate Pheno™ system, sub-cultured for purity on trypticase soy agar (TSA) plates, and images were taken with Sphere FLASH®. Antimicrobial susceptibility test (AST) results were compared to historical results from the broth microdilution (BMD) reference method. Quality control testing for the Accelerate PhenoTest™ BC kit was performed daily using the Accelerate PhenoTest™ BC ID and AST QC tests.

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

Performance Evaluation:
- Study Type: Internal performance evaluation study.
- Sample Size: 131 characterized Pseudomonas aeruginosa isolates (144 total isolates including original clinical trial isolates).
- Data Source: Internal study at Accelerate Diagnostics, Inc. Isolates seeded into BD BACTEC™ Plus Aerobic blood culture bottles.
- Annotation Protocol: Samples from positive blood culture bottles were Gram-stained, run on the Accelerate Pheno™ system, sub-cultured for purity on trypticase soy agar (TSA) plates, and images were taken with Sphere FLASH®. AST results compared to historical broth microdilution (BMD) reference method.
- Key Results:
  - Out of 115 tested samples in Phase 1, 113 produced positive identification for P. aeruginosa. 13 of these were excluded from AST analysis due to invalid results.
  - In Phase 2, all experiments resulted in valid data points for all five beta lactam antimicrobials, except five isolates which were retested.
  - Primary objective was to produce adequate essential and categorical agreement for ATM, CAZ, FEP, MEM, and TZP P. aeruginosa assays.
  - AST performance met all acceptance criteria for aztreonam.
  - For ceftazidime, all acceptance criteria were met except for the very major discrepancy rate, which was 7.9% (adjusted to 2.6% based on essential agreement and lack of an intermediate breakpoint).
  - For cefepime, very major and major discrepancy rates were 2.8%. Adjusted major error rate is 1.9% and adjusted very major error rate is 0%.
  - Meropenem met all AST criteria except for categorical agreement at 88.2%, attributed to minor errors.
  - Daily quality control test results were all within the expected MIC range.
Reproducibility Testing:
- Study Type: Internal reproducibility study conducted according to FDA's AST Class II Special Controls guidance.
- Sample Size: Isolates selected such that the complete set contained at least ten isolates per antimicrobial (aztreonam, cefepime, ceftazidime, meropenem and piperacillin-tazobactam) whose modal MIC result could be expected to be on-scale.
- Data Source: Isolates cultured from frozen stock and used to spike blood culture bottles were incubated until positive on a BD BACTEC® blood culture monitoring system.
- Annotation Protocol: On each day of testing, three samples from the same positive blood culture bottle were run on three separate Accelerate Pheno™ systems. Positive blood cultures were additionally sub-cultured for purity on trypticase soy agar plates. QC testing was conducted on each day using the Accelerate PhenoTest™ BC AST QC test. Best and worst-case EA rates were calculated.
- Key Results:
  - Reproducibility was >= 95% for all antimicrobials with P. aeruginosa, except for piperacillin-tazobactam (92.3% best case, 89.7% worst case).
  - Removal of two highly variable P. aeruginosa isolates for piperacillin-tazobactam yielded 96.4% best case and 93.3% worst case reproducibility.
  - All daily QC runs produced passing results.

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

Essential Agreement (EA), Categorical Agreement (CA), Very Major Error (vmj), Major Error (maj), Minor Error (min) are reported.
ATM: %EA=93.8, %CA=93.1, %vmj=0, %maj=1.0, %min=6.3.
FEP: %EA=95.1, %CA=92.3, %vmj=2.8, %maj=9.3. (Adjusted %vmj=0, %maj=1.9).
CAZ: %EA=96.5, %CA=96.5, %vmj=7.9, %maj=1.9. (Adjusted %vmj=2.6).
MEM: %EA=94.4, %CA=88.2, %vmj=0, %maj=2.0, %min=10.4.
TZP: %EA=96.4, %CA=94.2, %vmj=0, %maj=0, %min=5.8.

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.

Accelerate PhenoTest™ BC kit/Accelerate Pheno™ system (DEN160032)

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

§ 866.1650 A cellular analysis system for multiplexed antimicrobial susceptibility testing.

(a)
Identification. A cellular analysis system for multiplexed antimicrobial susceptibility testing is a multiplex qualitative and/or quantitative in vitro diagnostic device intended for the identification and determination of the antimicrobial susceptibility results of organisms detected in samples from patients with suspected microbial infections. This device is intended to aid in the determination of antimicrobial susceptibility or resistance when used in conjunction with other laboratory findings.(b)
Classification. Class II (special controls). The special controls for this device are:(1) Design verification and validation must include:
(i) Detailed device description documentation, including the device components, ancillary reagents required but not provided, a detailed explanation of the methodology, including primer/probe sequence, design, rationale for sequence selection, and details of the antimicrobial agents, as applicable.
(ii) Detailed documentation from the following analytical and clinical performance studies: limit of detection, inclusivity, precision, reproducibility, interference, cross-reactivity, carryover, and cross-contamination, quality control and additional studies, as applicable to specimen type and assay intended use.
(iii) Detailed documentation from an appropriate clinical study. The study, performed on a study population consistent with the intended use population, must compare the device performance to results obtained from well-accepted reference methods.
(iv) Detailed documentation for device software, including software applications and hardware-based devices that incorporate software.
(2) The labeling required under § 809.10(b) of this chapter must include:
(i) Limitations and protocols regarding the need for correlation of results by standard laboratory procedures, as applicable.
(ii) A detailed explanation of the interpretation of results and acceptance criteria.
(iii) A detailed explanation of the principles of operation and procedures for assay performance and troubleshooting.

Summary

Image /page/0/Picture/0 description: The image contains the logos of the U.S. Department of Health & Human Services and the U.S. Food & Drug Administration (FDA). The Department of Health & Human Services logo is on the left and features a stylized human figure. The FDA logo is on the right and includes the FDA acronym in a blue square, followed by the words "U.S. FOOD & DRUG ADMINISTRATION" in blue text.

September 15, 2020

Accelerate Diagnostics, Inc. Carrene Plummer Director, Regulatory Affairs 3950 S. Country Club Road #470 Tucson, Arizona 85714

Re: K192665

Trade/Device Name: Accelerate Pheno System, Accelerate PhenoTest BC Kit Regulation Number: 21 CFR 866.1650 Regulation Name: Positive Blood Culture Identification and AST Kit Regulatory Class: Class II Product Code: PRH, NSU, PEO, PAM, PEN, LON Dated: September 22, 2019 Received: September 25, 2019

Dear Carrene Plummer:

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/cfpmp/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 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 (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 https://www.fda.gov/medical-device-safety/medical-device-reportingmdr-how-report-medical-device-problems.

For comprehensive regulatory information about medical devices and radiation-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,

Ribhi Shawar, Ph.D. (ABMM) Chief General Bacteriology and Antimicrobial Susceptibility Branch 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

Indications for Use

510(k) Number (if known) K192665

Device Name Accelerate PhenoTest™ BC kit Accelerate Pheno™ system

Indications for Use (Describe)

The Accelerate PhenoTest™ BC kit identifies the following Gram-positive and Gram-negative bacteria and yeasts utilizing FISH probes targeting organism-specific ribosomal RNA sequences:

Staphylococcus aureus, Staphylococcus lugdunensis, Coagulase-negative Staphylococcus species (i.e., Staphylococcus epidermidis, Staphylococcus haemolyticus, Staphylococcus capits, Staphylococcus lugdunensis, Staphylococcus warneri, not differentiated), Enterococcus faecum, Streptococus spp. (i.e., Streptococus mitis, Streptococcus oralis, Streptococcus gallolyticus, Streptococcus agalactiae, Streptococus pneumoniae, not differentiated), Pseudomonas aeruginosa, Acinetobacter baumannii, Klebsiella pneumoniae, Klebsiella oxytoca, not differentiated), Escherichia coli, Enterobacter cloacae, Enterobacter (Klebsiella) aerogenes, not differentiated), Proteus mirabilis, Proteus vulgaris, not differentiated), Citrobacter spp. (i.e., Citrobacter koseri, not differentiated), Serratia marcescens, Candida albicans and Candida glabrata.

The Accelerate PhenoTest™ BC kit tests the following antimicrobial agents with the specific target organisms identified below:

Amikacin: Pseudomonas aeruginosa, Acinetobacter baumannii, Klebsiella pneumoniae, Klebsiella oxytoca, not differentiated), Escherichia coli, Enterobacter cloacae, Enterobacter (Klebsiella) aerogenes, not differentiated), Proteus mirabilis, Proteus vulgaris, not differentiated), Citrobacter spp. (i.e., Citrobacter freundii, Citrobacter koseri, not differentiated) and Serratia marcescens

Ampicillin: Enterococcus faecalis and Enterococcus faecium

Aztreonam: Pseudomonas aeruginosa, Klebsiella spp. (i.e., Klebsiella pneumoniae, Klebsiella oxytoca, not differentiated), Escherichia coli, Enterobacter spp. (i.e., Enterobacter (Klebsiella) aerogenes, not differentiated), Proteus spp. (i.e., Proteus mirabilis, Proteus vulgaris, not differentiated), Citrobacter freundii, Citrobacter koseri, not differentiated) and Serratia marcescens

Ceftazidime: Pseudomonas aeruginosa, Klebsiella pneumoniae, Klebsiella pneumoniae, Klebsiella oxytoca, not differentiated), Escherichia coli, Enterobacter spp. (i.e., Enterobacter (Klebsiella) aerogenes, not differentiated), Proteus spp. (i.e., Proteus vulgaris, not differentiated), Citrobacter spp. (i.e., Citrobacter freundii, Citrobacter koseri, not differentiated) and Serratia marcescens

Ceftaroline: Staphylococcus aureus

Cefepime: Pseudomonas aeruginosa, Klebsiella pneumoniae, Klebsiella oxytoca, not differentiated), Escherichia coli, Enterobacter spp. (i.e., Enterobacter (Klebsiella) aerogenes, not differentiated), Proteus spp. (i.e., Proteus mirabilis, Proteus vulgaris, not differentiated), Citrobacter freundii,

Citrobacter koseri, not differentiated) and Serratia marcescens

Ceftriaxone: Klebsiella spp. (i.e., Klebsiella pneumoniae, Klebsiella oxytoca, not differentiated), Escherichia coli, Enterobacter spp. (i.e., Enterobacter (Klebsiella) aerogenes, not differentiated), Proteus spp. (i.e., Proteus mirabilis, Proteus vulgaris, not differentiated), Citrobacter freundii, Citrobacter koseri, not differentiated) and Serratia marcescens

Ciprofloxacin: Pseudomonas aeruginosa, Klebsiella spp. (i.e., Klebsiella pneumoniae, Klebsiella oxytoca, not differentiated), Escherichia coli, Enterobacter spp. (i.e., Enterobacter (Klebsiella) aerogenes, not differentiated), Proteus spp. (i.e., Proteus vulgaris, not differentiated), Citrobacter spp. (i.e., Citrobacter freundii, Citrobacter koseri, not differentiated) and Serratia marcescens

Ertapenem: Klebsiella spp. (i.e., Klebsiella pneumoniae, Klebsiella oxytoca, not differentiated), Escherichia coli, Enterobacter spp. (i.e., Enterobacter (Klebsiella) aerogenes, not differentiated), Proteus spp. (i.e., Proteus mirabilis, Proteus vulgaris, not differentiated), Citrobacter freundii, Citrobacter koseri, not differentiated) and Serratia marcescens

Gentamicin: Pseudomonas aeruginosa, Klebsiella spp. (i.e., Klebsiella pneumoniae, Klebsiella oxytoca, not differentiated), Escherichia coli, Enterobacter spp. (i.e., Enterobacter (Klebsiella) aerogenes, not differentiated), Proteus spp. (i.e., Proteus vulgaris, not differentiated), Citrobacter spp. (i.e., Citrobacter freundii, Citrobacter koseri, not differentiated) and Serratia marcescens

Linezolid: Staphylococcus aureus, Enterococcus faecalis and Enterococcus faecium

Meropenem: Pseudomonas aeruginosa, Klebsiella spp. (i.e., Klebsiella pneumoniae, Klebsiella oxytoca, not differentiated), Escherichia coli, Enterobacter spp. (i.e., Enterobacter (Klebsiella) aerogenes, not differentiated), Proteus spp. (i.e., Proteus vulgaris, not differentiated), Citrobacter spp. (i.e., Citrobacter freundii, Citrobacter koseri, not differentiated) and Serratia marcescens

Piperacillin/Tazobactam: Pseudomonas aeruginosa, Acinetobacter baumannii, Klebsiella pneumoniae, Klebsiella oxytoca, not differentiated), Escherichia coli, Enterobacter cloacae, Enterobacter (Klebsiella) aerogenes, not differentiated), Proteus mirabilis, Proteus vulgaris, not differentiated), Citrobacter spp. (i.e., Citrobacter koseri, not differentiated) and Seratia marcescens Tobramycin: Pseudomonas aeruginosa, Klebsiella spp. (i.e., Klebsiella pneumoniae, Klebsiella oxytoca, not differentiated), Escherichia coli, Enterobacter spp. (i.e., Enterobacter (Klebsiella) aerogenes, not differentiated), Proteus spp. (i.e., Proteus vulgaris, not differentiated), Citrobacter spp. (i.e., Citrobacter freundii, Citrobacter koseri, not differentiated) and Serratia marcescens

Vancomycin: Staphylococcus aureus. Staphylococcus lugdunensis. Coagulase- negative Staphylococcus species (i.e., Staphylococcus epidermidis, Staphylococcus haemolyticus, Staphylococus hominis, Staphylococcus capitis, Staphylococus lugdunensis, Staphylococus warneri, not differentiated), Enterococcus faecius and Enterococus faccium

The following resistance phenotype is reported based on qualitative tests: Methicillin-resistance (S. aureus S. Jugdunensis, coagulase negative staphylococci).

Standard laboratory protocols for processing positive blood cultures should be followed to ensure availability of isolates for supplemental testing as needed. Additionally, subculture of positive blood culture is necessary for the identification and susceptibility testing of: organisms not identified by the Accelerate PhenoTest™ BC kit, organisms present in polymicrobial samples, organisms for which species identification is critical for patient care (e.g. speciation of Streptococus spp.), samples for which an "indeterminate" result for any probe was obtained, for testing antimicrobial agents not included on the Accelerate panel and for epidemiologic testing.

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)

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Image /page/5/Picture/0 description: The image shows the logo for Accelerate Diagnostics. The logo consists of a blue geometric shape on the left, followed by the word "ACCELERATE" in gray, block letters. Below "ACCELERATE" is the word "DIAGNOSTICS" in a smaller, blue font with a trademark symbol.

K192665
September 10, 2020

510(k) Summary

Image /page/6/Picture/0 description: The image shows the logo for Accelerate Diagnostics. The logo features a blue geometric shape on the left, resembling a stylized diamond or hexagon. To the right of the shape is the word "ACCELERATE" in a bold, sans-serif font. Below "ACCELERATE" is the word "DIAGNOSTICS" in a smaller, lighter blue font.

510(k) SUMMARY

Submitter Information:

Submitter: Accelerate Diagnostics, Inc.

Address: 3950 S. Country Club Road #470 Tucson, AZ 85714

Establishment Registration No: 3010671651

Contact Person: Carrene Plummer

Phone: (520) 405-1462

Fax: (520) 269-6580

E-mail: cplummer@axdx.com

Date Prepared: September 22, 2019

Name of Device and Classification:

Trade Name: Accelerate PhenoTest™ BC kit, Accelerate Pheno™ system

Classification Name: A cellular analysis system for multiplexed antimicrobial susceptibility testing

Product Code: PRH, NSU, PEO, PAM, PEN, LON

Predicate Device:

Accelerate PhenoTest™ BC kit/Accelerate Pheno™ system (DEN160032)

Image /page/7/Picture/0 description: The image shows the logo for Accelerate Diagnostics. The logo consists of a blue geometric shape on the left, followed by the word "ACCELERATE" in gray, sans-serif font. Below "ACCELERATE" is the word "DIAGNOSTICS" in a smaller, blue, sans-serif font with a trademark symbol.

Device Description

Assay Description

There are no changes to the description of the assays in the Accelerate PhenoTest™ BC kit description provided in DEN160032, except for updated time to result and addition of an optical filter to assist in removal of interfering sample debris.

Automated Sample Preparation

Automated sample preparation is performed using gel electrofiltration (GEF) which is based on gel electrophoresis principles. Sample is automatically transferred to a gel well containing pores smaller than bacterial or yeast cells. Application of an electric field causes lysed blood cells and/or other sample debris to pass into the gel wall while bacterial/yeast cells remain inside the gel well. The electric field is briefly reversed to dislodge bacterial/yeast cells from the gel wall prior to removal.

Cell Capture

Following sample preparation, recovered cells are automatically pipetted into multiple flowcell channels of the test cassette. Conductive layers of transparent indium tin oxide (TTO) coat the top and bottom inner surfaces of each flowcell channel and act as electrodes. An additional cationic poly-L-lysine layer on the bottom of each flowcell acts as a capture surface. When a voltage is applied, the negatively-charged bacterial/yeast cells migrate to the positively-charged capture surface where they are captured prior to imaging.

Image /page/8/Picture/0 description: The image shows the logo for Accelerate Diagnostics. The logo features a blue and gray geometric shape on the left, followed by the word "ACCELERATE" in gray, sans-serif font. Below "ACCELERATE" is the word "DIAGNOSTICS" in a smaller, blue, sans-serif font with a trademark symbol.

Fluorescence in situ Hybridization (FISH) for Identification

Cocktails of ATTO-532 (green) fluorescently-labeled DNA probes bind to the ribosomal RNA of target organisms following permeabilization. Each cocktail also includes ATTO-647 (red) labeled universal bacterial probe that binds to the ribosomal RNA of all clinically relevant bacteria (bacterial ID channels) or universal eukaryotic probe that binds to the ribosomal RNA of all clinically relevant yeast (yeast ID channels). The system images each flowcell using a fluorescence and dark-field microscope with camera and a filter set that captures emission from the FISH ID probes at 532 nm. 647 nm and in dark-field. An additional filter, capturing emission at 720 nm, is utilized prior to FISH ID for removal of interfering sample debris. To further exclude debris, only dark-field objects colocalized with universal probe signal are included in analysis. Colocalization of target probe signal and universal probe signal identifies a target organism.

The software also quantitates the total number of organisms present in a sample using a nucleic acid stain in a separate control flowcell. Comparing the relative numbers of each target organism to the number of objects lit up by the universal probes allows the system to differentiate bacteria/yeast from debris. FISH ID results are reported approximately 2 hours after loading the sample, and the ID result determines the selection of appropriate antimicrobials for subsequent antimicrobial susceptibility testing.

Morphokinetic Cellular Analysis (MCA) for Antimicrobial Susceptibility Testing (AST)

The Accelerate Pheno™ system leverages Morphokinetic Cellular Analysis (MCA) technology to measure distinct morphokinetic features of live microbial cells responding to antimicrobials to generate susceptibility results.

MCA is a computer vision based analytical method that uses digital microscopy inputs and machine learning technology to observe individual live cells and microcolonies (or clones) and recognize patterns of change over time. This technology tracks and analyzes multiple morphological and kinetic changes of individual cells and microcolonies under a variety of conditions. These changes include morphokinetic features such as cell morphology, mass as measured by light intensity of a growing microcolony, division rate, anomalous growth patterns, and heterogeneity.

Prior to AST, the remaining sample is combined with growth media and undergoes a pregrowth step during the FISH ID assay to normalize growth rates. Following automated sample preparation, the cells are quantitated and dynamically diluted to the appropriate concentration for AST testing. The cells are then captured in flowcell channels and

Image /page/9/Picture/0 description: The image shows the logo for Accelerate Diagnostics. The logo consists of a blue geometric shape on the left, followed by the word "ACCELERATE" in gray, block letters. Below "ACCELERATE" is the word "DIAGNOSTICS" in a smaller, lighter blue font. The logo is simple and modern, with a focus on the company name.

immobilized when growth media containing single concentrations of each test antimicrobial are added to separate flowcell channels. The bacteria in each flowcell are imaged every 10 minutes for up to 4.5 hours, creating a time-lapse record of bacterial growth from individual progenitor cells into clones of daughter cells.

During this period, morphokinetic features are measured and used for analysis. The precise quantitative measurement of individual clone growth rate over time is a powerful indicator of antimicrobial efficacy. Onboard software algorithms derive minimum inhibitory concentration (MIC) values from the measured features, and apply appropriate expert rules for proper interpretation and reporting of categorical interpretations - S, I or R (susceptible, intermediate, or resistant).

The Accelerate Pheno™ system is designed to perform Accelerate PhenoTest™ BC kit identification (ID) of bacterial and yeast cells and antimicrobial susceptibility testing (AST) in approximately 7 hours directly from positive blood culture samples. Depending on the computer configuration, up to eight ID/AST modules can be operated concurrently. Analysis time may increase when four or more tests are performed on ID/AST modules simultaneously. Other factors, such as samplexity, the number of organisms and/or antimicrobials available in the panel, may also increase time to result.

Quality Control

The Accelerate PhenoTest™ BC ID and AST OC tests automate the external QC testing procedure, removing the manual standardized inoculum preparation and manual dispensing of the McFarland standardized inoculum (0.5 for bacteria and 2.0 for fungi). This reduces the complexity of QC testing, eliminating the need for a clinical scientist to perform the test. Furthermore, the stability of the analyte is increased through the use of complementary sequences coupled to polymer microspheres for each of the target probes in the Accelerate PhenoTest™ BC kit.

As accessories to the Accelerate PhenoTest™ BC kit and Accelerate Pheno™ system, the Accelerate PhenoTest™ BC ID and AST QC tests have their own instructions for use.

Instrument Description

Changes to the instrument description provided in the de novo submission (DEN160032) include the addition of an alternate computing system (Interface PC/Analysis module) that supports up to 8 modules and change in time to result.

Image /page/10/Picture/0 description: The image shows the logo for Accelerate Diagnostics. The logo consists of a blue geometric shape on the left, followed by the word "ACCELERATE" in gray, block letters. Below "ACCELERATE" is the word "DIAGNOSTICS" in smaller, blue letters with a trademark symbol.

The Accelerate Pheno™ system is a fully-integrated in vitro diagnostic system comprised of one to eight ID/AST module(s), a computing system, touchscreen monitor and Accelerate Pheno™ system software for use with Accelerate PhenoTest™ kits. It is designed to perform identification (ID) of bacterial and yeast cells and antimicrobial susceptibility testing (AST) in approximately 7 hours directly from positive blood culture samples. Depending on the computer configuration, up to eight ID/AST modules can be operated concurrently. Analysis time may increase when four or more tests are initiated on ID/AST modules simultaneously. Other factors, such as sample complexity, the number of organisms and/or antimicrobials available in the assay kit panel, may also increase time to result.

Identification uses fluorescence in situ hybridization (FISH) and susceptibility testing uses microscopic observation of individual, live, growing bacterial cells in near real time (approximately every 10 minutes) in the presence of antimicrobial agents.

The Accelerate Pheno™ system is comprised of the following hardware:

Accelerate Pheno™ system ID/AST modules (Up to 4 or 8 depending on . computing system architecture)
Computing system, either: ●
- Control PC/Analysis PC setup (supports up to 4 ID/AST modules): o
  - ▪
  - 1 Analysis PC
- Interface PC/Analysis module setup (supports up to 8 ID/AST modules): o
  - 1 Interface PC .
  - . 1 Analysis module
Touchscreen monitor ●
Keyboard ●
Mouse ●
Power cords ●
. Cables
Uninterruptible Power Supply (1 UPS for up to 4 ID/AST modules and 1 UPS per ● computing system)

Each system contains up to 4 or 8 ID/AST modules (depending on computing system) and each ID/AST module can run one patient sample at a time. Each ID/AST module may be started or stopped at any time, independent of the other ID/AST modules.

Image /page/11/Picture/0 description: The image shows the logo for Accelerate Diagnostics. The logo features a blue geometric shape on the left, followed by the word "ACCELERATE" in gray, sans-serif font. Below "ACCELERATE" is the word "DIAGNOSTICS" in a smaller, blue, sans-serif font with a trademark symbol.

Software Description

There are no changes to the description of the Accelerate Pheno™ system software provided in DEN160032. The Accelerate Pheno™ system uses web-based software that controls system functions. The software can be accessed via the touchscreen monitor interface or remotely on a computer or device that has a web browser with network access to the host PC.

Intended Use/Indications for Use

The following changes have been made to the intended use/indications for use of the Accelerate PhenoTest™ BC kit since DEN160032: addition of the Pseuodomonas aeruginosa aztreonam assay, addition of newly recognized nomenclature for Enterobacter aerogenes, removal of macrolide-lincosamide-streptogramin B resistance (MLSb), and removal of erythromycin.

The Accelerate PhenoTest™ BC kit identifies the following Gram-positive and Gramnegative bacteria and yeasts utilizing FISH probes targeting organism-specific ribosomal RNA sequences:

Image /page/12/Picture/0 description: The image shows the logo for Accelerate Diagnostics. The logo consists of a blue geometric shape on the left, followed by the word "ACCELERATE" in gray, sans-serif font. Below "ACCELERATE" is the word "DIAGNOSTICS" in a smaller, blue, sans-serif font with a trademark symbol.

Citrobacter koseri, not differentiated), Serratia marcescens, Candida albicans and Candida glabrata.

The Accelerate PhenoTest™ BC kit tests the following antimicrobial agents with the specific target organisms identified below:

Ampicillin: Enterococcus faecalis and Enterococcus faecium

Ceftaroline: Staphylococcus aureus

Image /page/13/Picture/0 description: The image shows the logo for Accelerate Diagnostics. The logo features a blue and gray geometric shape on the left, followed by the word "ACCELERATE" in gray, sans-serif font. Below "ACCELERATE" is the word "DIAGNOSTICS" in a smaller, blue, sans-serif font with a trademark symbol.

mirabilis, Proteus vulgaris, not differentiated), Citrobacter spp. (i.e., Citrobacter freundii, Citrobacter koseri, not differentiated) and Serratia marcescens

Linezolid: Staphylococcus aureus, Enterococcus faecalis and Enterococcus faecium

Tobramycin: Pseudomonas aeruginosa, Klebsiella spp. (i.e., Klebsiella pneumoniae,

Image /page/14/Picture/0 description: The image shows the logo for Accelerate Diagnostics. The logo consists of a blue geometric shape on the left, resembling a stylized molecule or network. To the right of the shape is the company name, "ACCELERATE," in a bold, sans-serif font. Below "ACCELERATE" is the word "DIAGNOSTICS" in a smaller, lighter blue font, with a trademark symbol next to it.

Klebsiella oxytoca, not differentiated), Escherichia coli, Enterobacter spp. (i.e., Enterobacter cloacae, Enterobacter (Klebsiella) aerogenes, not differentiated), Proteus spp. (i.e., Proteus mirabilis, Proteus vulgaris, not differentiated), Citrobacter spp. (i.e., Citrobacter freundii, Citrobacter koseri, not differentiated) and Serratia marcescens

Vancomycin: Staphylococcus aureus, Staphylococcus lugdunensis, Coagulasenegative Staphylococcus species (i.e., Staphylococcus epidermidis, Staphylococcus haemolyticus, Staphylococcus hominis, Staphylococcus capitis, Staphylococcus lugdunensis, Staphylococcus warneri, not differentiated), Enterococcus faecalis and Enterococcus faecium

The following resistance phenotype is reported based on a qualitative test: Methicillinresistance (S. aureus S. lugdunensis, coagulase negative staphylococci).

Image /page/15/Picture/0 description: The image shows the logo for Accelerate Diagnostics. The logo features a blue and gray geometric shape on the left, followed by the word "ACCELERATE" in a sans-serif font. Below "ACCELERATE" is the word "DIAGNOSTICS" in a smaller, lighter blue font with a trademark symbol.

Comparison of Technological Characteristics with the Predicate Device

Similarities
Item	Device	Predicate
	Accelerate PhenoTestTM BC Kit	Accelerate PhenoTestTM
BC Kit (DEN160032)
Intended Use	The Accelerate PhenoTestTM BC kit is a multiplexed in vitro diagnostic test utilizing both qualitative nucleic acid fluorescence in situ hybridization (FISH) identification and quantitative, antimicrobial susceptibility testing (AST) methods and is intended for use with the Accelerate PhenoTM system. The Accelerate PhenoTestTM BC kit is capable of simultaneous detection and identification of multiple microbial targets followed by susceptibility testing of the appropriate detected bacterial organisms. The Accelerate PhenoTestTM BC kit is performed directly on blood culture samples identified as positive by a continuous monitoring blood culture system. Results are intended to be interpreted in conjunction with Gram stain results.	Same
Similarities
Item	Device	Predicate
	Accelerate PhenoTest™ BC Kit	Accelerate PhenoTest™
BC Kit (DEN160032)
Organisms Identified	The Accelerate PhenoTest™ BC
kit identifies the following Gram-
positive and Gram-negative
bacteria and yeasts utilizing FISH
probes targeting organism-
specific ribosomal RNA
sequences: Staphylococcus
aureus, Staphylococcus
lugdunensis, Coagulase-negative
Staphylococcus species
(Staphylococcus epidermidis,
Staphylococcus haemolyticus,
Staphylococcus hominis,
Staphylococcus capitis,
Staphylococcus lugdunensis,
Staphylococcus warneri, not
differentiated), Enterococcus
faecalis, Enterococcus faecium,
Streptococcus spp. (Streptococcus
mitis, Streptococcus oralis,
Streptococcus gallolyticus,
Streptococcus agalactiae,
Streptococcus pneumoniae, not
differentiated), Pseudomonas
aeruginosa, Acinetobacter
baumannii, Klebsiella spp.
(Klebsiella pneumoniae,
Klebsiella oxytoca, not
differentiated), Escherichia coli,
Enterobacter spp. (Enterobacter
cloacae, Enterobacter	Same
Similarities
Item	Device
Accelerate PhenoTest™ BC Kit	Predicate
Accelerate PhenoTest™
BC Kit (DEN160032)
	(Klebsiella) aerogenes, not
differentiated), Proteus spp.
(Proteus mirabilis, Proteus
vulgaris, not differentiated),
Citrobacter spp. (Citrobacter
freundii, Citrobacter koseri, not
differentiated), Serratia
marcescens, Candida albicans
and Candida glabrata.
Sample	Positive Blood Culture as
identified by a continuous
monitoring blood culture system	Same
Reagent Cartridge	Accelerate PhenoTest™ BC kit	Same
Instrument	Accelerate Pheno™ system	Same

Table 1: Predicate Device Comparison Similarities

Image /page/16/Picture/0 description: The image shows the logo for Accelerate Diagnostics. The logo consists of a blue geometric shape on the left, followed by the word "ACCELERATE" in gray, block letters. Below "ACCELERATE" is the word "DIAGNOSTICS" in a smaller, light blue font with a trademark symbol.

Image /page/17/Picture/0 description: The image shows the logo for Accelerate Diagnostics. The logo consists of a blue and gray geometric shape on the left, followed by the word "ACCELERATE" in gray, block letters. Below the word "ACCELERATE" is the word "DIAGNOSTICS" in a smaller, blue font with a trademark symbol.

Table 1: Predicate Device Comparison Differences

Differences
Item	Device	Predicate
	Accelerate PhenoTestTM BC
Kit	Accelerate PhenoTestTM
BC Kit (DEN160032)
Antimicrobial Agents	Double concentrations of
aztreonam, cefepime,
ceftazidime and piperacillin
tazobactam for Pseudomonas
aeruginosa testing	Single concentrations of
aztreonam, cefepime,
ceftazidime and piperacillin
tazobactam
Differences
Item	Device
Accelerate PhenoTest™ BC
Kit	Predicate
Accelerate PhenoTest™
BC Kit (DEN160032)
Test Kit	Removal of MLSb and
erythromycin	Included MLSb and
erythromycin
	Accelerate PhenoTest™ BC kit,
enhanced wet reagent well
(consolidated wells)	Accelerate PhenoTest™ BC
kit, wet reagent well
External Quality Control
Assays	Accelerate PhenoTest™ BC ID
and AST QC test(s)	Manual QC assay
ATCC QC Organisms
Maintenance	No QC organism maintenance
required	Users required to maintain
all 20 QC strains required
for testing
QC Sample Preparation	Automated QC inoculum
preparation and standardization
performed by the Accelerate
Pheno™ system	User prepares standardized
inoculum of each QC strain
and manually dispenses into
designated wells in the
Accelerate PhenoTest™ BC
kit
Accessories/Materials
Required But Not
Provided For External QC
Testing	Accelerate PhenoTest™ BC ID
and AST QC test(s)	QC Assay Loading
"Template Tool"
		ATCC QC organism(s)
35°C (+/- 2) Incubator with
CO2
		Trypticase soy agar (TSA)
plates containing 5%
sheep's blood (BAP) (for
bacteria growth)
Sabouraud Dextrose plates
(for yeast growth)
Differences
Item	Device
Accelerate PhenoTest™ BC Kit	Predicate
Accelerate PhenoTest™ BC Kit (DEN160032)
		Commercially prepared
Trypticase soy broth (TSB) with no additives
		Commercially available, calibrated turbidity meter
		0.5 and 2.0 McFarland
Standards for use with commercially available
turbidity meter
		Falcon® 5mL Round
Bottom Polystyrene Test
Tubes with Snap Cap,
Sterile (Corning Product # 352054) or equivalent
Test Interpretation and
Results Reporting	Modified Expert rules	Original Expert rules from
DEN160032
	ID Interpretive Rules increase
reporting of the monomicrobial
call and decreases incidence of
indeterminate calls and
ambiguous results due to
debris/noise	Original Monomicrobial
Indeterminate and false
positive in DEN160032
	AO Bright Rule improves
overall reportability by
decreasing invalid results	Original invalid results in
DEN160032
Differences
Item	Device
Accelerate PhenoTestTM BC Kit	Predicate
Accelerate PhenoTestTM BC Kit (DEN160032)
	Noise Rejection analysis decreases by-run false positive rate of clinical stock isolates	By-run false positive rate for clinical stock isolates in DEN160032
	Improved ID target detection thresholds	Original normal hit, bright rule and high sensitivity detection in DEN160032
	MEM algorithm changes decrease MIN error rate for PAE	Original MIN error rate for PAE
Time to Result	ID Results ~2 hours
AST Results ~7 hours	ID Results ~1.5 hours
AST Results ~6.5 hours
Instrument	Optical set submitted in DEN160032 with additional far-red filter	Optical set submitted in DEN160032
Computing System	Add Interface PC/Analysis module setup (supports up to 8 ID/AST modules)	Control PC/Analysis PC setup (supports up to 4 ID/AST modules)
Software Algorithms	Add ID interpretive rules, AO bright rule, and ID algorithm improvements. Updated algorithms for aztreonam, cefepime, ceftazidime, meropenem and piperacillin-tazobactam with P. aeruginosa	Original algorithms for aztreonam, cefepime, ceftazidime, meropenem and piperacillin-tazobactam with P. aeruginosa
Software Algorithms	Accelerate PhenoTM system software includes noise rejection analysis using far red filter to reject interfering debris	Noise rejection analysis using far red filter to reject interfering debris not performed
Differences
Item	Device
Accelerate PhenoTest™ BC
Kit	Predicate
Accelerate PhenoTest™
BC Kit (DEN160032)
Software QC Assays	Accelerate Pheno™ system
software automates QC testing
for ID and AST using the
Accelerate PhenoTest™ BC
ID/AST QC tests	QC assays performed by
Accelerate Pheno™ system
requires manual dispensing
of standardized inoculum
into designated wells of
Accelerate PhenoTest™ BC
kit

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Image /page/19/Picture/0 description: The image shows the logo for Accelerate Diagnostics. The logo features a blue geometric shape on the left, resembling a stylized hexagon or diamond. To the right of the shape, the word "ACCELERATE" is written in a bold, sans-serif font. Below "ACCELERATE", the word "DIAGNOSTICS" is written in a smaller, lighter font.

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Image /page/22/Picture/0 description: The image shows the logo for Accelerate Diagnostics. The logo features a blue geometric shape on the left, resembling a stylized diamond or hexagon made up of smaller shapes. To the right of the shape is the company name, "ACCELERATE," in a bold, sans-serif font. Below "ACCELERATE" is the word "DIAGNOSTICS" in a smaller, sans-serif font, with a trademark symbol next to it.

Performance Data

Performance data are provided within this premarket notification in support of the substantial equivalence determination.

Electrical safety and electromagnetic compatibility (EMC)

Electrical safety and EMC testing is identical to that conducted for the predicate device. The Accelerate Pheno™ system complies with IEC 61010-1:2010, Safety requirements for electrical equipment for measurement, control, and laboratory use- Part 1: General requirements, and also with IEC 60601-1-2:2014, medical electrical equipment: General requirements for basic safety and essential performance - Collateral Standard: Electromagnetic disturbances - Requirements and tests.

Software Verification and Validation Testing

Software verification and validation testing were conducted and documentation is provided as recommended by FDA's Guidance for Industry and FDA Staff, "Guidance for the Content of Premarket Submissions for Software Contained in Medical Devices." The software for this device was considered to have a "moderate" level of concern, since a failure or latent flaw could indirectly result in minor injury to the patient or operator through incorrect or delayed information or through the action of a care provider.

Non-Clinical Test Summaries

Performance Evaluation

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microdilution (BMD) reference method. Quality control testing for the Accelerate PhenoTest™ BC kit was performed daily using the Accelerate PhenoTest™ BC ID and AST QC tests.

During the Phase 1 performance evaluation study, a total of 113 out of the 115 tested samples produced a positive identification for Pseudomonas aeruginosa. Two of the P. aeruginosa samples produced negative or off-panel ID calls and were excluded from analysis per study exclusion criteria. Of the 113 positive P. aeruginosa samples, 13 did not proceed to AST testing due to invalid results (e.g., growth control channel failures) and were additionally excluded from data analysis. In Phase 2, aside from five isolates that were retested once each due to ID failures, all experiments resulted in valid data points for all five beta lactam antimicrobials.

The primary objective of the clinical evaluation study for the Accelerate PhenoTest™ BC kit aztreonam, ceftazidime, meropenem and piperacillin-tazobactam Pseudomonas aeruginosa assays was to produce adequate essential and categorical agreement. At least two two-fold dilutions below the susceptible and one two-fold dilution above the resistant threshold as specified in the FDA Class II Special Controls Guidance document were tested over the Accelerate Pheno™ system reportable ranges of ≤2 µg/mL to ≥64 µg/mL (ATM, CAZ, FEP), ≤1 µg/mL to ≥16 µg/mL (MEM), ≤4 ug/mL to ≥256 ug/mL (TZP). Table 3 provides an overall summary of AST performance for the two testing phases plus analysis of the 13 original clinical isolates for the Accelerate PhenoTest™ BC kit aztreonam, cefepime, ceftazidime, meropenem and piperacillin-tazobactam Pseudomonas aeruginosa assays.

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K192665 September 9, 2020

| Abx | Reporting
Range | N | #EA | %EA | N
(Eval) | #EA
(Eval) | %EA
(Eval) | #CA | %CA | #R | #S | #vmj | %vmj | #maj | %maj | #min | %min |
|----------|--------------------|-----|-----|------|-------------|---------------|---------------|-----|------|----|-----|------|------|------|------|------|------|
| ATMa | 2-64 | 144 | 135 | 93.8 | 73 | 64 | 87.7 | 134 | 93.1 | 35 | 105 | 0 | 0 | 1 | 1.0 | 9 | 6.3 |
| FEPa,b,d | 2-64 | 143 | 136 | 95.1 | 40 | 33 | 82.5 | 132 | 92.3 | 36 | 107 | 1 | 2.8 | 10 | 9.3 | N/A | N/A |
| CAZa,c | 2-64 | 141 | 136 | 96.5 | 30 | 25 | 83.3 | 136 | 96.5 | 38 | 103 | 3 | 7.9 | 2 | 1.9 | N/A | N/A |
| MEMa,d,e | 1-16 | 144 | 136 | 94.4 | 25 | 17 | 68.0 | 127 | 88.2 | 25 | 102 | 0 | 0 | 2 | 2.0 | 15 | 10.4 |
| TZPa | 4-256 | 138 | 133 | 96.4 | 27 | 22 | 81.5 | 130 | 94.2 | 30 | 101 | 0 | 0 | 0 | 0 | 8 | 5.8 |

Table 2: Accelerate PhenoTest™ BC kit Assay Performance Summary

"Using an expanded reference range, EA was reduced as to last of EA for very high or very low MICs: aztreonam 91.0%, ceferine 83.2%, piperacillin-tazobactam 93.5%, meropenem 93.1%.

The observed major eror rates for cefepine when testing P. aeruginosa are 9.3% and 2.8% respectively. Based on the essential and lack of an internediate breakpoint for cefepime, the adjusted major error rate is 1.9% and the adjusted very major error rate is 0%.

The observed very major error rate for cefazione when is 7.9%. Based on the essential agreement and lack of an internetiate breakpoint for ceftazione, the adjusted very major error rate is 2.6%.

"When not in evact agreement, of essults for P. aernginosa ended to be at least one doubling dilution higher than the reference method, which increass the potential for major errors.

6The observed low category agreement was due to the occurrence of a high number of minor errors.

AST performance met all acceptance criteria for azteonam. For ceftazidime. all acceptance criteria were met except for the very major discrepancy rate, which was 3/38 (7.9%). However, based on the essential ack of an intermediate breakpoint for ceftazidime, the adjusted very major error rate is 2.6%. For cefepine, all acceptance criteria were met except for the very major and major discrepancy rates, which were 1/36 (2.8%), respectively. However, based on the essential agreement and lack of an intermediate breakpoint for cefepime, the adjusted major error rate is 1.9% and the adjusted very major error rate is 0%. Meropenem met all AST accept for categorical agreement at 127/144 (88.2%). Low categorical agreement for meropenem was attributed to the occurrence of minor errors. Daily quality control test results were all within the expected MIC range for each of the five antimicrobials.

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Reproducibility Testing

An internal reproducibility study was conducted according to FDA's AST Class II Special Controls guidance. Isolates were selected such that the complete set contained at least ten isolates per antimicrobial (aztreonam, cefepime, ceftazidime, meropenem and piperacillintazobactam) whose modal MIC result could be expected to be on-scale. Isolates were cultured from frozen stock and used to spike blood culture bottles were incubated until positive on a BD BACTEC® blood culture monitoring system. On each day of testing, three samples from the same positive blood culture bottle were run on three separate Accelerate Pheno™ systems. The same three systems were used for each isolate on all days of testing. Positive blood cultures were additionally sub-cultured for purity on trypticase soy agar plates, which were incubated at 35°C for 18-24 hours. QC testing was conducted on each day of reproducibility testing using the Accelerate PhenoTest™ BC AST QC test. Best and worst-case EA rates were calculated for each antimicrobial-isolate combination as well as for each antimicrobial across all isolates whose modal MIC result for the same antimicrobial was on-scale. Best-case EA rate with the modal result was expected to be at least 95%.

As shown in Table 4 below, reproducibility was ≥95% for all antimicrobials with P. aeruginosa, with the exception of piperacillin-tazobactam. For this antimicrobial, two P. aeruginosa isolates were found to be highly variable in their response to piperacillintazobactam. Removal of these isolates provided 96.4% best case and 93.3% worst case results. All daily QC runs produced passing results.

	Best Case	Best Case	Worst Case	Worst Case
Antibiotic	Totals	Percentage	Totals	Percentage
Aztreonam	171/180	95.0%	165/180	91.7%
Ceftazidime	143/150	95.3%	134/150	89.3%
Cefepime	175/180	97.2%	175/180	97.2%
Meropenem	115/120	95.8%	105/120	87.5%
Piperacillin-
tazobactamª	180/195	92.3%	175/195	89.7%

Table 4: Reproducibility of AST assay for P. aeruginosa with beta lactams; Best and Worst Case Reproducibility

4Two P. aeruginosa isolates were found to be highly variable in their response to piperacillin-tazobactam; removal of these isolates provided the following reproducibility results: best case 96.4%, worst case 93.3%.

Clinical Study Summary

No clinical testing was performed to support a substantial equivalence determination for the aztreonam, cefepime, ceftazidime, meropenem and piperacillin-tazobactam assay modifications.