← Product Code [QZX](/submissions/MI/subpart-b%E2%80%94diagnostic-devices/QZX) · K244044

# PBC Separator with Selux AST System (K244044)

_Selux Diagnostics, Inc. · QZX · Mar 28, 2025 · Microbiology · SESE_

**Canonical URL:** https://fda.innolitics.com/submissions/MI/subpart-b%E2%80%94diagnostic-devices/QZX/K244044

## Device Facts

- **Applicant:** Selux Diagnostics, Inc.
- **Product Code:** [QZX](/submissions/MI/subpart-b%E2%80%94diagnostic-devices/QZX.md)
- **Decision Date:** Mar 28, 2025
- **Decision:** SESE
- **Submission Type:** Traditional
- **Regulation:** 21 CFR 866.1650
- **Device Class:** Class 2
- **Review Panel:** Microbiology

## Indications for Use

The Selux AST System is intended to be used for the automated quantitative or qualitative susceptibility testing for most clinically significant aerobic microorganisms. The Selux AST System does not provide organism identification.

## Device Story

The PBC Separator is an automated instrument for preparing bacterial inocula from positive blood culture bottles. It processes samples from continuous monitoring blood culture systems (e.g., BACTEC, BacT/ALERT) using lysis, centrifugation, and sequential optical density measurements to achieve a tuned McFarland-equivalent suspension. The device is used in clinical laboratories by technicians. The resulting inoculum is transferred to the Selux AST System, which incubates samples and quantifies microbial growth in a 384-well panel to determine minimum inhibitory concentrations (MICs). The system requires manual or LIS-downloaded organism identification to interpret susceptibility results. The device enables faster AST results (under 7 hours) compared to traditional methods, aiding clinicians in selecting appropriate antimicrobial therapy for patients with bloodstream infections.

## Clinical Evidence

Clinical performance was evaluated using 247 clinical (64 fresh, 183 seeded) and 75 challenge isolates across three sites. Performance was compared to broth microdilution reference methods. Essential Agreement (EA) and Categorical Agreement (CA) were calculated for various antimicrobial-organism combinations. Results showed high EA (mostly >94%) and CA (mostly >96%) across tested gram-positive organisms (Enterococci, S. aureus). Reproducibility studies (intra- and inter-site) demonstrated ≥94% agreement. Interfering substances (endogenous/exogenous) showed minimal impact on performance.

## Technological Characteristics

Automated sample preparation instrument using lysis, centrifugation, and on-board spectrophotometry for optical density measurement. 384-well panel format for AST. Connectivity: Networked to site workstation. Software: Embedded firmware (v70.0) and Selux AST System software (v1.12). Sterilization: Not applicable (consumables). Standards: IEC 60601-1-2, ANSI UL 61010-1, IEC 62304, ISO 14971.

## Regulatory 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.

## Special Controls

*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.

## Predicate Devices

- PBC Separator with Selux AST System ([K223493](/device/K223493.md))

## Submission Summary (Full Text)

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>
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FDA

U.S. FOOD & DRUG

ADMINISTRATION

# 510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY

ASSAY AND INSTRUMENT

## I Background Information:

A 510(k) Number

K244044

B Applicant

Selux Diagnostics, Inc.

C Proprietary and Established Names

PBC Separator with Selux AST System

D Regulatory Information

|  Product Code(s) | Classification | Regulation Section | Panel  |
| --- | --- | --- | --- |
|  QZX | Class II | 21 CFR 866.1650 - A Cellular Analysis System For Multiplexed Antimicrobial Susceptibility | MI - Microbiology  |
|  LON | Class II | 21 CFR 866.1645 - Fully automated short-term incubation cycle antimicrobial susceptibility system | MI - Microbiology  |
|  LTT | Class II | 21 CFR 866.1640 - Antimicrobial susceptibility test powder | MI - Microbiology  |
|  LTW | Class II | 21 CFR 866.1640 - Antimicrobial susceptibility test powder | MI - Microbiology  |

## II Submission/Device Overview:

### A Purpose for Submission:

To add additional claims of specific antimicrobial agents with specific gram-positive organisms to the previously cleared device, K223493 for the PBC Separator with the Selux AST System of specific antimicrobial agents with specific gram-negative organisms.

Food and Drug Administration

10903 New Hampshire Avenue

Silver Spring, MD 20993-0002

www.fda.gov

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K244044 - Page 2 of 26

B Measurand:

Standardized suspension of gram-positive bacteria prepared from positive blood culture samples used in conjunction with the Selux AST System with the following antimicrobial agents:

|  Antimicrobial | Reportable Range  |
| --- | --- |
|  Ampicillin | ≤2 to ≥64  |
|  Ceftaroline | ≤0.25 to ≥16  |
|  Daptomycin | ≤0.25 to ≥32  |
|  Linezolid | ≤0.5 to ≥32  |
|  Oxacillin | ≤0.5 to ≥16  |
|  Vancomycin | ≤0.5 to ≥64  |
|  Cefoxitin Screen
(mecA oxacillin resistance) | SN or SP  |

C Type of Test:

Positive blood culture (PBC) processor that prepares an inoculum for use with the Selux AST System, a quantitative antimicrobial susceptibility test system that utilizes colorimetric, oxidation-reduction, and growth-based strategies to determine the minimum inhibitory concentration (MIC) of specific antimicrobial agents for specific organisms.

III Intended Use/Indications for Use:

A Intended Use(s):

The Selux AST System is intended to be used for the automated quantitative or qualitative susceptibility testing for most clinically significant aerobic microorganisms. The Selux AST System does not provide organism identification.

B Indication(s) for Use:

The PBC Separator with Selux AST System is an automated inoculum preparation system that uses lysis, centrifugation and sequential optical density measurements to generate a McFarland equivalent suspension from positive blood culture samples that can be used for quantitative in vitro antimicrobial susceptibility testing by the Selux AST System. Samples are processed directly from blood culture samples identified as positive by a continuous monitoring blood culture system. Samples should be confirmed as monomicrobial, gram negative rods or gram positive cocci by Gram stain. Organism identification is required for AST result interpretation and reporting, per the Selux AST System instructions for use.

Inoculum preparation by the PBC Separator was evaluated for use with the Selux AST System and the Selux AST Gram Negative Panel. Performance was demonstrated for the antimicrobial agents and organisms identified below:

Amikacin: Acinetobacter baumannii complex, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa

Amoxicillin-Clavulanate: Escherichia coli, Klebsiella species (including K. oxytoca, K. pneumoniae), Proteus mirabilis, Proteus vulgaris

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Ampicillin: Escherichia coli, Proteus mirabilis

Ampicillin-Sulbactam: Acinetobacter baumannii complex, Citrobacter koseri, Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis

Cefazolin: Escherichia coli, Klebsiella pneumoniae

Cefepime: Citrobacter freundii complex, Citrobacter koseri, Enterobacter cloacae complex, Escherichia coli, Klebsiella aerogenes, Klebsiella oxytoca, Klebsiella pneumoniae, Morganella morganii, Proteus mirabilis, Proteus vulgaris, Serratia marcescens, Pseudomonas aeruginosa

Ceftazidime: Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa

Ceftazidime-Avibactam: Citrobacter freundii complex, Citrobacter koseri, Enterobacter cloacae complex, Escherichia coli, Klebsiella aerogenes, Klebsiella oxytoca, Klebsiella pneumoniae, Morganella morganii, Proteus mirabilis, Proteus vulgaris, Serratia marcescens, Pseudomonas aeruginosa

Ceftriaxone: Citrobacter freundii complex, Citrobacter koseri, Enterobacter cloacae complex, Escherichia coli, Klebsiella aerogenes, Klebsiella oxytoca, Klebsiella pneumoniae, Proteus mirabilis, Serratia marcescens

Ciprofloxacin: Citrobacter freundii complex, Citrobacter koseri, Enterobacter cloacae complex, Escherichia coli, Klebsiella aerogenes, Klebsiella oxytoca, Klebsiella pneumoniae, Morganella morganii, Proteus mirabilis, Proteus vulgaris, Serratia marcescens, Pseudomonas aeruginosa

Ertapenem: Citrobacter freundii complex, Citrobacter koseri, Enterobacter cloacae complex, Escherichia coli, Klebsiella aerogenes, Klebsiella oxytoca, Klebsiella pneumoniae, Morganella morganii, Proteus mirabilis, Proteus vulgaris, Serratia marcescens

Gentamicin: Citrobacter freundii complex, Citrobacter koseri, Enterobacter cloacae complex, Escherichia coli, Klebsiella aerogenes, Klebsiella oxytoca, Klebsiella pneumoniae, Morganella morganii, Proteus mirabilis, Proteus vulgaris, Serratia marcescens, Pseudomonas aeruginosa

Imipenem: Acinetobacter baumannii complex, Escherichia coli, Klebsiella pneumoniae

Meropenem: Acinetobacter baumannii complex, Citrobacter freundii complex, Citrobacter koseri, Enterobacter cloacae complex, Escherichia coli, Klebsiella oxytoca, Klebsiella pneumoniae, Morganella morganii, Proteus mirabilis, Proteus vulgaris, Serratia marcescens, Pseudomonas aeruginosa

Minocycline: Acinetobacter baumannii complex, Escherichia coli, Klebsiella pneumoniae

Piperacillin-Tazobactam: Acinetobacter baumannii complex, Citrobacter koseri, Escherichia coli, Klebsiella pneumoniae, Morganella morganii, Proteus mirabilis, Proteus vulgaris, Serratia marcescens, Pseudomonas aeruginosa

Tobramycin: Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa

K244044 - Page 3 of 26

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Inoculum preparation by the PBC Separator was evaluated for use with the Selux AST System and the Selux AST Gram Positive Panel. Performance was demonstrated for the antimicrobial agents and organisms identified below:

Ampicillin: Enterococcus faecalis, Enterococcus faecium

Ceftaroline: Staphylococcus aureus

Daptomycin: Enterococcus faecalis, Enterococcus faecium, Staphylococcus aureus

Linezolid: Enterococcus faecalis, Enterococcus faecium, Staphylococcus aureus

Oxacillin: Staphylococcus aureus

Vancomycin: Enterococcus faecalis, Enterococcus faecium, Staphylococcus aureus

The PBC Separator with Selux AST System Gram-Positive Panel is a qualitative test for the following antimicrobial agents with the specific target organisms identified below:

Cefoxitin Screen to predict mecA-mediated oxacillin resistance: Staphylococcus aureus

Susceptibility test 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 susceptibility testing of organisms present in polymicrobial samples, for testing antimicrobial agents and species not indicated for testing with the device, for epidemiologic testing, and for recovery of organisms present in microbial samples.

## C Special Conditions for Use Statement(s):

Rx - For Prescription Use Only

- The PBC Separator with Selux AST System cannot be used for any clinical specimens other than monomicrobial positive blood cultures.
- Performance of PBC Separator-prepared inoculum for use with the Selux AST System has only been established using the antimicrobials listed in the Indications for Use.
- Results from the Selux AST System obtained using inocula prepared by the PBC Separator should only be reported for antimicrobials and species indicated in the PBC Separator with Selux AST System Indications for Use.
- The use of the PBC Separator with Selux AST System does not eliminate the need for subculture of the positive blood culture.
- If the subculture (purity) plate indicates the sample is polymicrobial, the AST results should be voided, and susceptibility testing on each isolate using a standard inoculum preparation should be performed.
- The performance of the PBC Separator with Selux AST System has only been evaluated with the following blood culture bottles:

- BD BACTEC Plus Aerobic
- BD BACTEC Plus Anaerobic
- BD BACTEC Standard Aerobic
- BD BACTEC Standard Anaerobic

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- BD BACTEC Lytic Anaerobic
- BD BACTEC Peds Plus
- bioMérieux BacT/ALERT FA Plus Aerobic
- bioMérieux BacT/ALERT FN Plus Anaerobic
- bioMérieux BacT/ALERT SA Standard Aerobic
- bioMérieux BacT/ALERT SN Standard Anaerobic
- bioMérieux BacT/ALERT PF Plus Pediatric Aerobic

- PBC samples should be promptly prepared and loaded into the PBC Separator following bottle ring from a continuous monitoring blood culture system, where possible. In the case of instrument errors or if re-testing is needed, PBC samples must be processed within 16 hours post bottle ring.
- The tuned inoculum must be used within 45 minutes to maintain the appropriate organism concentration.
- The following limitations were added to the device labeling based on performance demonstrated in the current submission:
- An essential agreement < 90% and a major error was observed when testing Linezolid with S. aureus with the potential interferent conjugated bilirubin.
- An essential agreement < 90% was observed when testing Vancomycin with E. faecalis with the potential interferent Cefpodoxime.
- An essential agreement < 90% was observed when testing Vancomycin with E. faecalis with the potential interferent Penicillin.
- The ability of the PBC Separator and Selux AST system to detect resistance in the following antimicrobial/organism combinations is unknown because an insufficient number of resistant/ non-susceptible isolates were available at the time of comparative testing.
- Ampicillin: E. faecalis
- Ceftaroline: S. aureus
- Daptomycin: E. faecalis, E. faecium, S. aureus
- Linezolid: Enterococcus spp.
- Vancomycin: S. aureus

## D Special Instrument Requirements:

PBC Separator, software version 70.0 (instrument firmware)

Selux AST System, software version 1.12

## IV Device/System Characteristics:

## A Device Description:

The PBC Separator with Selux AST System is an automated sample preparation instrument with associated consumables that uses lysis, centrifugation, and sequential optical density measurements to prepare tuned McFarland-equivalent suspensions from positive blood culture (PBC) bottles that register as positive on a continuous monitoring blood culture system. Inoculums containing monomicrobial, gram-positive bacteria are used for antimicrobial susceptibility testing (AST) processing with the Selux AST System.

K244044 - Page 5 of 26

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![img-0.jpeg](img-0.jpeg)
Figure 1. The PBC Separator with Selux AST System (left), Selux AST System Inoculator (center), and Selux AST System Analyzer (right).

![img-1.jpeg](img-1.jpeg)

![img-2.jpeg](img-2.jpeg)

The PBC Separator is comprised of the instrument, software, and associated consumables. Within a biosafety cabinet,  $9\mathrm{mL}$  of the PBC bottle is transferred to the Selux Sample Tube. The Sample Tube is loaded into the PBC Separator along with an empty final Inoculum Tube and the PBC Separator Reagent Kit. The software also prompts the user to load racks of pipette tips. The PBC Separator Reagent Kit serves as the waste receptacle into which all biohazardous waste is deposited during the separation process and can be disposed of appropriately after processing. After the samples are loaded, the user follows the prompts on the user interface to start processing, which requires 45 to 60 minutes based on if one or two samples are being processed. The PBC Separator software associates the barcode identifier on the Inoculum Tube with the barcode identifier on the Sample Tube and transmits this information to the Selux Site Services central workstation to ensure sample traceability. Within the instrument, the PBC Separator uses a series of centrifugation and lysis steps to remove blood and most soluble components. Saline is added and optical density is determined to achieve a density suitable for AST. The PBC Separator contains embedded software and a graphical user interface that guides users through the workflow. The user is notified when the sample processing is completed and is prompted to retrieve the sample components. Once processing of the sample is complete, the user then manually transfers the tuned inoculum in the final Inoculum Tube (a volume of  $1\mathrm{mL}$ ) to the Selux AST System for further AST processing. If insufficient microorganisms are present to prepare the suspension to the required range, the PBC Separator will alert the user that processing was unsuccessful, and the sample will not be accepted by the Selux AST System.

The Selux AST System includes a Sample Prep Station (i.e., AST Workbench), an Inoculator, an Analyzer, a Workbench Computer containing the Selux Site Software, and the reagents and consumables required to perform AST testing. The PBC Separator and all Selux AST System components are connected to a site workstation, which coordinates sample processing on all instruments. A complete description of the Selux AST System can be found in the K211759 and K211748 decision summaries.

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The PBC Separator with the Selux AST System utilizes the Selux Gram Positive Panel, a 384-well panel that provides parallel results for the antimicrobials indicated for each sample type. The Selux AST System software masks non-indicated results.

The reportable MIC ranges are shown in Table 1 below.

Table 1. Reportable MIC Ranges and Organism-Specific Breakpoints for Antimicrobials Tested with the PBC Separator with Selux AST System.

|  Antimicrobial | Indicated Organism Group | Selux AST System Reportable Range (μg/mL) | FDA-Recognized/Approved Breakpoints* (μg/mL)  |   |   |   |
| --- | --- | --- | --- | --- | --- | --- |
|   |   |   |  S | SDD | I | R  |
|  Ampicillin | Enterococci | ≤2 to ≥64 | ≤8 | - | - | ≥16  |
|  Ceftaroline | Staphylococcus aureus | ≤0.25 to ≥16 | ≤1 | 2-4 | - | ≥8  |
|  Daptomycin | Enterococcus faecium | 1 to ≥32 | - | ≤4 | - | ≥8  |
|   |  Enterococcus faecalis | ≤1 to ≥32 | ≤2 | - | 4 | ≥8  |
|   |  Staphylococcus aureus | ≤0.25 to ≥8 | ≤1 | - | - | -  |
|  Linezolid | Enterococci | ≤0.5 to ≥16 | ≤2 | - | 4 | ≥8  |
|   |  Staphylococcus aureus | ≤1 to ≥32 | ≤4 | - | - | ≥8  |
|  Oxacillin | Staphylococcus aureus | ≤0.5 to ≥16 | ≤2 | - | - | ≥4  |
|  Vancomycin | Enterococci | ≤1 to ≥64 | ≤4 | - | 8-16 | ≥32  |
|   |  Staphylococcus aureus | ≤0.5 to ≥32 | ≤2 | - | 4-8 | ≥16  |
|  Cefoxitin Screen (mecA oxacillin resistance) | Staphylococcus aureus | SN or SP | NA | NA | NA | NA  |

S, Susceptible; SDD, Susceptible-Dose Dependent I, Intermediate; R, Resistant; (-) Indicates that a corresponding MIC is not defined for that category; NA: FDA breakpoints not applicable because Cefoxitin Screen is a qualitative test based on a single test concentration value of  $4\mu \mathrm{g} / \mathrm{mL}$  with results reported either as SN (screen negative) or SP (screen positive).
* FDA STIC Website https://www.fda.gov/drugs/development-resources/fda-recognized-antimicrobial-susceptibility-test-interpretive-criteria.

# B Principle of Operation:

The PBC Separator automatically prepares a tuned bacterial inoculum directly from a blood culture bottle that signal positive on an FDA-cleared continuous monitoring blood culture system, including the Becton Dickinson BACTEC, the bioMérieux BacT/Alert 3D, and the bioMérieux BacT/Alert Virtuo. The PBC Separator removes contaminants through multi-step centrifugation-wash cycles and specific buffer lysis of mammalian cells. The PBC Separator utilizes an on-board spectrometer to tune the inoculum for the right cell density to perform AST.

Tuned inoculums are used with the Selux AST System. The Selux AST System performs AST similarly to the reference broth microdilution (BMD) method by first incubating samples, then quantifying microbial growth in each well of an antimicrobial dilution series after a growth period, and finally determining the minimum inhibitory concentration (MIC) by comparing growth data in each well.

The PBC Separator with Selux AST System can only provide AST results for monomicrobial samples. Since the PBC Separator with Selux AST System does not perform species-level identification (ID), the monomicrobial nature of the sample must be confirmed by an FDA-cleared direct-from-positive blood culture ID system. While PBC Separator processing can be performed without ID, this information is required for the Selux AST System to interpret and report susceptibility results because the MIC-determining algorithm is species-specific as is the

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interpretative Susceptible (S), Susceptible Dose Dependent (SDD), Intermediate (I), or Resistant (R) determination. Species ID can be performed by any appropriate method, and this information can be either manually input to the Selux AST System or automatically downloaded from the laboratory information system (LIS) once the sample ID is entered into the LIS. Any FDA-cleared method may be used to provide an ID including biochemical techniques, matrix-assisted laser desorption/ionization mass spectrometry, and multiplex genetic assays.

AST testing of PBC samples requires that the Gram type (classification) of the organism be known prior to testing on the Selux AST System as the information is necessary to select the proper AST panel to use. Gram stain information is not needed to start sample processing with the PBC Separator.

## C Instrument Description Information:

1. Instrument Name:

PBC Separator with Selux AST System

2. Specimen Identification:

Gram stain analysis is performed prior to AST testing to select the appropriate panel but is not required prior to processing with the PBC Separator. Identification (ID) using an FDA-cleared method is required prior to result interpretation and reporting after Selux AST System processing.

To ensure sample traceability, the PBC Separator software associates the barcode identifier on the Inoculum Tube with the barcode identifier on the Sample Tube and transmits this information to the Selux Site Services central workstation.

Refer to the K211759 Decision Summary for additional information on the Selux AST System.

3. Specimen Sampling and Handling:

Positive blood culture (PBC) samples must be processed immediately after ringing positive on a continuous monitoring blood culture system or within 16 hours of positivity should delays be unavoidable. The user aseptically transfers 9 mL of PBC from the blood bottle into the Selux Sample Tube. The user then loads the Sample Tube, Inoculum Tube, and Reagent Kit into the PBC Separator and runs the process using the graphical interface on the instrument. After processing, the Inoculum Tube is collected and used with the downstream Selux AST System, following the instructions for use for that system.

Refer to the K211759 Decision Summary for additional information on the Selux AST System.

4. Calibration:

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The PBC Separator on-board spectrophotometer is calibrated by a trained service engineer at the time of installation. Additional weekly or as-needed calibrations should be performed by the user by following the QC workflow in the instructions for use (described below).

Refer to the K211759 Decision Summary for additional information on the Selux AST System.

## 5. Quality Control:

Quality controls are performed to ensure that the PBC Separator works according to the intended use and performance specifications. The spectrophotometer within the PBC Separator should be calibrated weekly or as required. Following the PBC Separator Quality Control Verification procedure in the instructions for use, the user will initiate the PBC Separator QC workflow on the instrument interface. McFarland standards provided with the instrument (0.0 and 0.5 standards) are inserted into the spectrophotometer and three readings are taken, with the tube being rotated and re-inserted between each reading. The average readings for the 0.5 McFarland standard should be within the acceptable ranges defined in the instructions for use (0.44 to 0.56). The instructions for use outlines the steps to follow depending on the average readings obtained.

Quality control for AST testing should be conducted in accordance with the instructions for use for the Selux AST System and Gram-Positive Panel. Refer to the Decision Summary for K211759 for additional information.

## V Substantial Equivalence Information:

### A Predicate Device Name(s):

PBC Separator with Selux AST System

### B Predicate 510(k) Number(s):

K223493

### C Comparison with Predicate(s):

|  Device & Predicate Device(s): | K244044
(Candidate Device) | K223493
(Predicate Device)  |
| --- | --- | --- |
|  Device Trade Name | PBC Separator with Selux AST System | PBC Separator with Selux AST System  |
|  General Device Characteristic Similarities  |   |   |
|  Intended Use/Indications For Use | The PBC Separator with Selux AST System is an automated inoculum preparation system that uses lysis, centrifugation and sequential optical density measurements to generate a McFarland equivalent suspension from positive blood culture samples that can be used for quantitative in vitro antimicrobial susceptibility testing by the Selux AST System. Samples are processed directly from blood culture samples identified as positive by a | The PBC Separator with Selux AST System is an automated inoculum preparation system that uses lysis, centrifugation and sequential optical density measurements to generate a McFarland-equivalent suspension from positive blood culture samples that can be used for quantitative in vitro antimicrobial susceptibility testing by the Selux AST System. Samples are processed directly from blood culture samples identified as positive by a  |

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|   | continuous monitoring blood culture system. Samples should be confirmed as monomicrobial, gram negative rods or gram positive cocci by Gram stain. Organism identification is required for AST result interpretation and reporting, per the Selux AST System instructions for use. | continuous monitoring blood culture system. Samples should be confirmed as monomicrobial, gram negative rods by Gram stain. Organism identification is required for AST result interpretation and reporting, per the Selux AST System instructions for use.  |
| --- | --- | --- |
|  Sample Type | Aliquot from monomicrobial positive blood culture | Same  |
|  Test Technology | Uses a series of lysis and centrifugation steps and sequential optical density measurements to generate a tuned McFarland equivalent inoculum. | Same  |
|  Test Output/ Results Reporting | Liquid suspension (McFarland equivalent) of bacteria suitable for downstream susceptibility testing | Same  |
|  Downstream Susceptibility Testing | Selux AST System | Same  |
|  General Device Characteristic Differences |  |   |
|  Indicated Antimicrobials | Includes new indications for use for: Ampicillin Ceftaroline Daptomycin Linezolid Oxacillin Vancomycin Cefoxitin Screen | Amikacin Amoxicillin-Clavulanate Ampicillin Ampicillin-Sulbactam Cefazolin Cefepime Ceftazidime Ceftazidime-Avibactam Ceftriaxone Ciprofloxacin Ertapenem Gentamicin Imipenem Meropenem Minocycline Piperacillin-Tazobactam Tobramycin  |
|  Indicated Organisms | Includes new indications for use for: Enterococcus faecalis Enterococcus faecium Staphylococcus aureus | Acinetobacter baumannii complex Citrobacter freundii complex Citrobacter koseri Enterobacter cloacae complex Escherichia coli Klebsiella spp. Morganella morganii Proteus mirabilis Proteus vulgaris Pseudomonas aeruginosa Serratia marcescens  |

VI Standards/Guidance Documents Referenced:

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|  Document # | Title  |
| --- | --- |
|  IEC 60601-1-2 Edition 4.1 2020-09 CONSOLIDATED VERSION | Medical electrical equipment - Part 1-2: General requirements for basic safety and essential performance - Collateral Standard: Electromagnetic disturbances - Requirements and tests  |
|  ANSI UL 61010-1 3^{rd} Edition dated May 12, 2012 with revision through July 19, 2019 | Standard for Safety for Electrical Equipment For Measurement, Control and Laboratory Use; Part 1: General Requirements  |
|  IEC 62304 Edition 1.1 2015-06 CONSOLIDATED VERSION | Medical device software - Software life cycle processes  |
|  CLSI M100 33^{rd} Edition | Performance Standards for Antimicrobial Susceptibility Testing  |
|  ISO 14971 Third Edition 2019-12 | Application of Risk Management to Medical Devices  |

## VII Performance Characteristics (if/when applicable):

### Analytical Performance:

#### 1. Precision/Reproducibility:

Precision/reproducibility was conducted to assess the performance of the PBC Separator with Selux AST System at three – one internal and two external – testing sites. Panel members included representative species from each organism group indicated for use with each claimed antimicrobial. Reproducibility was evaluated between sites (inter-site) and within sites (intra-site) and determined from the total number (and percent) of the modal MIC results that fell within $\pm$ one doubling dilution divided by the total number of results. Both best-case (assumes that off-scale results are within one dilution of the mode) and worst-case (assumes that off-scale results are more than one dilution of the mode) performance was determined for each antimicrobial, as outlined in the AST Special Controls Guidance¹. Acceptance criteria are $\geq 95\%$ best-case reproducibility and $\geq 89\%$ worst-case reproducibility for both inter-site and intra-site reproducibility. The results of cefoxitin screen are qualitative only (either positive or negative), so reproducibility was assessed based on a match of the qualitative results to the reference method. Test results were calculated as reproducible if they exactly matched the modal result of the isolate to assess reproducibility.

Gram-positive organisms were seeded into blood culture bottles containing healthy human donor blood and incubated in a continuous monitoring blood culture system until positivity. Inter-site reproducibility was evaluated at three sites by testing at least five representative isolates with on-scale MIC values for each antimicrobial, for a minimum of 135 results per antimicrobial (5 isolates $\times$ 3 sites $\times$ 3 replicates $\times$ 3 days = 135 results/antimicrobial). Testing was performed on three instruments, one instrument per site, and data from all three systems were combined to assess inter-site reproducibility. Best-case reproducibility was $\geq 95\%$, and worst-case inter-site reproducibility was $\geq 94\%$ and were determined to be acceptable.

¹ FDA Class II Special Controls Guidance Document: Antimicrobial Susceptibility Test (AST) Systems; Guidance for Industry and FDA (Issued August 28, 2009)

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Intra-site reproducibility was evaluated by testing a minimum of five representative isolates in triplicate on three days at one internal site for a minimum of 45 results per antimicrobial (5 isolates × 3 replicates × 3 days = 45 results/antimicrobial/site). Best-case and worst-case intra-site reproducibility were acceptable (≥ 97%).

Data from both studies are collated and summarized in Table 2 below. Since the cefoxitin screen is a qualitative only assay, results are not presented in the table. Cefoxitin reproducibility results were 134/135 (99.3%) and 45/45 (100%) for inter-site and intra-site reproducibility, respectively.

Table 2. Summary Results of Reproducibility Study of the PBC Separator with Selux AST System

|  Antimicrobial | Inter-site Reproducibility |   | Intra-site Reproducibility  |   |
| --- | --- | --- | --- | --- |
|   |  Best-case (%) | Worst-case (%) | Best-case (%) | Worst-case (%)  |
|  Ampicillin | 135/135 (100%) | 135/135 (100%) | 45/45 (100%) | 45/45 (100%)  |
|  Ceftaroline | 135/135 (100%) | 135/135 (100%) | 45/45 (100%) | 45/45 (100%)  |
|  Daptomycin | 270/270 (100%) | 270/270 (100%) | 90/90 (100%) | 90/90 (100%)  |
|  Linezolid | 269/270 (99.6%) | 269/270 (99.6%) | 89/90 (98.9%) | 89/90 (98.9%)  |
|  Oxacillin | 129/135 (95.5%) | 128/135 (94.8%) | 45/45 (100%) | 44/45 (97.8%)  |
|  Vancomycin | 243/243 (100%) | 243/243 (100%) | 81/81 (100%) | 81/81 (100%)  |

2. Linearity:
This study is not applicable.

3. Analytical Specificity/Interference:
An interfering substances study was performed to evaluate if substances naturally present or artificially introduced into blood culture bottles affected performance of the PBC Separator with Selux AST System. MIC results from PBC Separator-prepared samples were evaluated on the Selux AST System using seeded PBC samples with or without interfering substances. Studies were performed with *E. faecalis* and *S. aureus*, i.e., one organism from each reporting group, and were evaluated with each claimed antimicrobial. Endogenous and exogenous interferents were spiked into blood culture bottles at or above clinically relevant concentrations alongside bacteria and a volume of human blood. Bottles were processed with a continuous monitoring blood culture system until positivity and processed with the PBC Separator. As this is a method-to-method comparison, essential agreement (EA) of ≥ 95% was deemed acceptable. MIC results showed > 89.9% EA for every interferent tested. Instances in which EA was < 95% for specific interferents is discussed below.

Endogenous Interference
Performance with potential endogenous interferents is shown in Tables 3 and 4.

- Cefoxitin Screen was considered separately since it is qualitative only (either positive or negative). No interference was observed, i.e., results exactly matched the control (without interferent) result for all endogenous interferents.
- Linezolid when tested with Conjugated Bilirubin had an EA of 66.7% for *S. aureus*. A single replicate was out of EA and category agreement (CA), resulting in a major error. The following limitation will be included in the device labeling to address this error:

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An essential agreement  $< 90\%$  and a major error was observed when testing Linezolid with S. aureus with the potential interferent conjugated bilirubin.

- Linezolid when tested with Gamma Globulins had an EA of  $66.7\%$  for S. aureus. A single replicate was out of EA but was within CA, and thus is not expected to impact clinical care; the data are acceptable.
- Oxacillin when tested with Triglycerides had an EA of  $66.7\%$  for S. aureus. A single replicate was out of EA but was within CA, and thus is not expected to impact clinical care; the data are acceptable.

Table 3. Summary Performance Results with Potential Endogenous Interferents

|  Antimicrobial | Indicated Organism(s) | Red Blood Cells (20 g/dL) |   | White Blood Cells (12,000 cells/μL) |   | Platelets (450,000/μL)  |   |
| --- | --- | --- | --- | --- | --- | --- | --- |
|   |   |  # EA / Total | %EA | # EA / Total | %EA | # EA / Total | %EA  |
|  Ampicillin | Enterococci | 3/3 | 100.0% | 3/3 | 100.0% | 3/3 | 100.0%  |
|  Ceftaroline | Staphylococci | 3/3 | 100.0% | 3/3 | 100.0% | 3/3 | 100.0%  |
|  Daptomycin | Enterococci | 3/3 | 100.0% | 3/3 | 100.0% | 3/3 | 100.0%  |
|   |  Staphylococci | 3/3 | 100.0% | 3/3 | 100.0% | 3/3 | 100.0%  |
|   |  Combined | 6/6 | 100.0% | 6/6 | 100.0% | 6/6 | 100.0%  |
|  Linezolid | Enterococci | 3/3 | 100.0% | 3/3 | 100.0% | 3/3 | 100.0%  |
|   |  Staphylococci | 3/3 | 100.0% | 3/3 | 100.0% | 3/3 | 100.0%  |
|   |  Combined | 6/6 | 100.0% | 6/6 | 100.0% | 6/6 | 100.0%  |
|  Oxacillin | Staphylococci | 3/3 | 100.0% | 3/3 | 100.0% | 3/3 | 100.0%  |
|  Vancomycin | Enterococci | 3/3 | 100.0% | 3/3 | 100.0% | 3/3 | 100.0%  |
|   |  Staphylococci | 3/3 | 100.0% | 3/3 | 100.0% | 3/3 | 100.0%  |
|   |  Combined | 6/6 | 100.0% | 6/6 | 100.0% | 6/6 | 100.0%  |

Table 4. Summary Performance Results with Potential Endogenous Interferents

|  Antimicrobial | Indicated Organism(s) | Conjugated Bilirubin (475 μmol/L) |   | Unconjugated Bilirubin (684 μmol/L) |   | Triglycerides (16.94 mmol/L) |   | Gamma Globulins (16.94 mmol/L)  |   |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
|   |   |  # EA / Total | %EA | # EA / Total | %EA | # EA / Total | %EA | # EA / Total | %EA  |
|  Ampicillin | Enterococci | 3/3 | 100.0% | 3/3 | 100.0% | 3/3 | 100.0% | 3/3 | 100.0%  |
|  Ceftaroline | Staphylococci | 3/3 | 100.0% | 3/3 | 100.0% | 3/3 | 100.0% | 3/3 | 100.0%  |
|  Daptomycin | Enterococci | 3/3 | 100.0% | 3/3 | 100.0% | 3/3 | 100.0% | 3/3 | 100.0%  |
|   |  Staphylococci | 3/3 | 100.0% | 3/3 | 100.0% | 3/3 | 100.0% | 3/3 | 100.0%  |
|   |  Combined | 6/6 | 100.0% | 6/6 | 100.0% | 6/6 | 100.0% | 6/6 | 100.0%  |
|  Linezolid | Enterococci | 3/3 | 100.0% | 3/3 | 100.0% | 3/3 | 100.0% | 3/3 | 100.0%  |
|   |  Staphylococci | 2/3 | 66.7% | 3/3 | 100.0% | 3/3 | 100.0% | 2/3 | 66.7%  |
|   |  Combined | 5/6 | 83.3% | 6/6 | 100.0% | 6/6 | 100.0% | 5/6 | 83.3%  |
|  Oxacillin | Staphylococci | 3/3 | 100.0% | 3/3 | 100.0% | 2/3 | 66.7% | 3/3 | 100.0%  |
|  Vancomycin | Enterococci | 3/3 | 100.0% | 3/3 | 100.0% | 3/3 | 100.0% | 3/3 | 100.0%  |
|   |  Staphylococci | 3/3 | 100.0% | 3/3 | 100.0% | 3/3 | 100.0% | 3/3 | 100.0%  |
|   |  Combined | 6/6 | 100.0% | 6/6 | 100.0% | 6/6 | 100.0% | 6/6 | 100.0%  |

# Exogenous Interferents

Performance with potential exogenous interferents is shown in Table 5.

- Cefoxitin Screen was considered separately since results are qualitative-only (positive or negative). No interference was observed, i.e., results exactly matched the control (without interferent) result for all exogenous interferents.

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- Vancomycin when tested with potential interferent Cefpodoxime had an EA of 33.3% for Enterococci. This was due to the inclusion of one strain of E. faecalis with two replicates that were out of EA but within CA. The following limitation will be included in the device labeling to address this error:
- An essential agreement < 90% was observed when testing Vancomycin with E. faecalis with the potential interferent Cefpodoxime.
- Vancomycin when tested with potential interferent Penicillin had an EA of 33.3% for Enterococci. This was due to the inclusion of one strain of E. faecalis with two replicates that were out of EA but within CA. The following limitation will be included in the device labeling to address this error:
- An essential agreement < 90% was observed when testing Vancomycin with E. faecalis with the potential interferent Penicillin.

Table 5. Summary Performance Results with Potential Exogenous Interferents

|  Antimicrobial | Indicated Organism(s) | Ciprofloxacin (3.6 μg/mL) |   | Cefpodoxime (2.3 μg/mL) |   | Gentamicin (6 μg/mL) |   | Penicillin (6 μg/mL)  |   |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
|   |   |  # EA / Total | %EA | # EA / Total | %EA | # EA / Total | %EA | # EA / Total | %EA  |
|  Ampicillin | Enterococci | 3/3 | 100.0% | 3/3 | 100.0% | 3/3 | 100.0% | 3/3 | 100.0%  |
|  Ceftaroline | Staphylococci | 3/3 | 100.0% | 3/3 | 100.0% | 3/3 | 100.0% | 3/3 | 100.0%  |
|  Daptomycin | Enterococci | 3/3 | 100.0% | 3/3 | 100.0% | 3/3 | 100.0% | 3/3 | 100.0%  |
|   |  Staphylococci | 3/3 | 100.0% | 3/3 | 100.0% | 3/3 | 100.0% | 3/3 | 100.0%  |
|   |  Combined | 6/6 | 100.0% | 6/6 | 100.0% | 6/6 | 100.0% | 6/6 | 100.0%  |
|  Linezolid | Enterococci | 3/3 | 100.0% | 3/3 | 100.0% | 3/3 | 100.0% | 3/3 | 100.0%  |
|   |  Staphylococci | 3/3 | 100.0% | 3/3 | 100.0% | 3/3 | 100.0% | 3/3 | 100.0%  |
|   |  Combined | 6/6 | 100.0% | 6/6 | 100.0% | 6/6 | 100.0% | 6/6 | 100.0%  |
|  Oxacillin | Staphylococci | 3/3 | 100.0% | 3/3 | 100.0% | 3/3 | 100.0% | 3/3 | 100.0%  |
|  Vancomycin | Enterococci | 3/3 | 100.0% | 1/3 | 33.3% | 3/3 | 100.0% | 1/3 | 33.3%  |
|   |  Staphylococci | 3/3 | 100.0% | 3/3 | 100.0% | 3/3 | 100.0% | 3/3 | 100.0%  |
|   |  Combined | 6/6 | 100.0% | 4/6 | 66.7% | 6/6 | 100.0% | 4/6 | 66.7%  |

4. Assay Reportable Range:
This study is not applicable.

5. Traceability, Stability and Expected Values (Controls, Calibrators, or Methods):

Quality Controls
Quality control (QC) testing was performed each day that analytical study testing was conducted. QC was performed at all clinical and reference sites each day that study samples were processed. Clinical sites followed the PBC Separator with Selux AST System IFU to perform QC on the PBC Separator and the Selux AST System IFU to perform QC on the Selux AST System (comprised of the Inoculator and Analyzer instruments). The reference site performed QC for BMD broth microdilution in accordance with the CLSI M07² and M100 documents. All QC results are summarized below.

PBC Separator QC
A 0.5 McFarland standard inoculum was measured on each instrument in use to confirm absorbance measurement accuracy according to the PBC Separator IFU. Triplicate OD

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readings of the 0.5 McFarland standard were averaged and compared to the acceptable range (0.44-0.56) to pass QC. QC readings were within the expected OD range for 100% of the measurements.

## Selux AST System QC

Selux AST System QC was conducted in accordance with the IFU with the Gram-Positive Panel. Three CLSI-recommended ATCC QC strains (E. faecalis ATCC 29212, S. aureus ATCC 29213, and S. aureus ATCC 43300) were seeded in blood culture bottles, incubated until positivity, and processed with the PBC Separator. Inoculums were used with the Gram-Positive Panel on the Selux AST System. Testing was conducted at three sites (two external, one internal). Performance was evaluated as the frequency with which test results were within the expected QC MIC range for each antimicrobial at each site. All antimicrobials demonstrated ≥ 95% of samples within the acceptable QC range at each site and cumulatively. The data are presented in Table 6.

Table 6. Performance of the PBC Separator with Selux AST System using QC Strains

|  Antimicrobial | QC Strain | Selux Dilution Range | Acceptable QC Range | Site 1 |   | Site 2 |   | Site 3 |   | All Sites  |   |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
|   |   |   |   |  N | % in Range | N | % in Range | N | % in Range | N | % in Range  |
|  Ampicillin | E. faecalis ATCC 29212 | ≤ 2 to ≥ 64 | 0.5-2 μg/mL | 46 | 100 | 45 | 100 | 35 | 100 | 126 | 100  |
|  Ceftaroline | S. aureus ATCC 29213 | ≤ 0.25 to ≥ 16 | 0.12-0.5 μg/mL | 45 | 100 | 45 | 100 | 34 | 100 | 124 | 100  |
|  Daptomycin | S. aureus ATCC 29213 | ≤ 0.25 to ≥ 32 | 0.12-1 μg/mL | 45 | 100 | 45 | 100 | 34 | 100 | 124 | 100  |
|  Linezolid | S. aureus ATCC 29213 | ≤ 0.5 to ≥ 32 | 1-4 μg/mL | 45 | 100 | 45 | 100 | 34 | 100 | 124 | 100  |
|  Oxacillin | S. aureus ATCC 29213 | ≤ 0.5 to ≥ 16 | 0.12-0.5 μg/mL | 45 | 100 | 45 | 100 | 34 | 100 | 124 | 100  |
|  Vancomycin | S. aureus ATCC 29213 | ≤ 0.5 to ≥ 64 | 0.5-2 μg/mL | 45 | 100 | 45 | 100 | 34 | 97.0 | 124 | 99.2  |
|  Cefoxitin Screen | S. aureus ATCC 29213 | SN or SP | Negative | 45 | 100 | 45 | 100 | 34 | 100 | 124 | 100  |
|   |  S. aureus ATCC 43300 | SN or SP | Positive | 47 | 97.9 | 45 | 100 | 35 | 100 | 127 | 99.2  |

## Inoculum Density Check

The PBC Separator has an onboard densitometer and liquid handler that prepares tuned inoculums for AST. Daily QC testing of the PBC Separator at clinical sites was done to verify that the onboard densitometer was able to consistently detect an 0.5 McFarland inoculum (see Quality Control Testing above), and results were acceptable.

To further verify the turbidity of prepared McFarland inoculums by the PBC Separator, quantitative culture was performed to determine the inoculum densities of all samples in the QC analytical study, all samples in the reproducibility study, and at least 10% of clinical isolates. Data were provided as CFU/mL at the final dilution used in the wells of the Selux AST Panel. The data are shown in Table 7. The concentration ranges and mean values obtained appear to be within the recommended ranges for the reference method and in accordance with the AST Special Controls Guidance and ranged from 1.6 × 10⁵ CFU/mL to 1.0 × 10⁶ CFU/mL in the sample well.

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Table 7. Concentrations of Inoculums prepared by the PBC Separator

|  Organism | Study Source | Number Tested | Sample Well Concentration (CFU/mL)  |   |
| --- | --- | --- | --- | --- |
|   |   |   |  Mean | Std. Dev.  |
|  E. faecalis ATCC 29212 | Clinical QC | 123 | 5.1E+05 | 2.16E+05  |
|  S. aureus ATCC 29213 | Clinical QC | 122 | 7.2E+05 | 2.28E+05  |
|  S. aureus ATCC 43300 | Clinical QC | 125 | 4.8E+05 | 1.83E+05  |
|  Enterococcus faecalis | Clinical, Reproducibility | 170 | 5.5E+05 | 2.55E+05  |
|  Enterococcus faecium | Clinical, Reproducibility | 88 | 3.8E+05 | 1.90E+05  |
|  Staphylococcus aureus | Clinical, Reproducibility | 216 | 1.5E+05 | 2.20E+05  |
|  E. faecalis ATCC 29212 | Reference QC | 44 | 4.1E+05 | 1.27E+05  |
|  S. aureus ATCC 29213 | Reference QC | 112 | 4.6E+05 | 1.33E+05  |
|  S. aureus ATCC 43300 | Reference QC | 19 | 3.8E+05 | 1.44E+05  |

## Device Failures

The PBC Separator is equipped with self-checking mechanisms to identify run errors. There were fifteen instrument failures observed during the clinical study. The failures were attributed to two failure modes, pipettor aspiration failure and tube gripping failure in the centrifuge.

## Purity Check

Purity plates were prepared from the inoculum suspensions of every sample tested. AST results were only reported for pure isolates; data generated from plates that generated multiple colony morphologies was excluded from analyses.

## Sample Stability

### Positive Blood Culture Stability

Testing was conducted to establish the stability of positive blood culture for use with the PBC Separator with Selux AST System. Blood bottles were seeded in triplicate with human blood and representative isolates (from each claimed antimicrobial/organism reporting group) and incubated to positivity on a continuous monitoring blood culture system (bioMérieux BACT/ALERT VIRTUO or BD BACTEC). After positivity, blood bottles were processed with the PBC Separator either immediately (0 h, baseline) or after storing at room temperature for 16 hours. MIC results were generated using PBC Separator-prepared inoculums with the Selux AST System. Results at the 16-hour and 18-hour timepoints were compared to modal MIC results at baseline (t=0) for each drug and organism reporting group. As this was a method-to-method comparison, EA ≥ 95% for each antimicrobial agent was considered acceptable. The total EA for all results at the 16-hour and 18-hour timepoints compared with the 0-hour timepoint was 100.0% (30/30 results in EA). As noted in the instructions for use, all blood culture bottle samples should be tested promptly after ringing positive on a continuous monitoring system. In the case of unavoidable delays or if the need for retesting arises, positive blood culture bottles may be tested up to 16 hours post ring.

### Inoculum Hold Time Stability

The amount of time between PBC Separator inoculum preparation and AST processing with the Selux AST System was evaluated. Selux AST System MIC results from samples

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processed after inoculum hold times of 30, 45 and 55 minutes were compared with samples processed after inoculum hold times of < 5 minutes. Three replicates of each indicated antimicrobial/organism reporting group were tested per timepoint. The total EA for all results at the 45-minute timepoint compared with the < 5-minute timepoint was 100.0% (30/30 results in EA). Selux AST System processing should be promptly initiated after PBC Separator processing is complete. In the case of unavoidable delays, PBC Separator-prepared inoculum may be held for up to 45 minutes before initiating Selux AST System processing.

6. Detection Limit:
This study is not applicable.

7. Assay Cut-Off:
This study is not applicable.

8. Accuracy (Instrument):
This study is not applicable.

9. Carry-Over:
Cross-contamination and carry-over with the PBC Separator with Selux AST System with the Gram-Negative Panel was previously assessed and deemed acceptable in K223493.
Cross-contamination and carry-over with the Inoculator and Analyzer components of the Selux AST System was previously assessed and deemed acceptable in K211759.

Comparison Studies:

1. Method Comparison with Reference Device:
Clinical performance testing was conducted with the PBC Separator with Selux AST System. Performance was evaluated using fresh positive blood culture (PBC) samples, PBC samples seeded with contemporary and stock clinical isolates, as well as PBC samples seeded with challenge isolates selected for their resistance profiles. Contemporary isolates were defined as isolates that had been collected, frozen and tested within six months of collection while stock isolates were tested six or more months after collection. Clinical isolates were collected from PBC bottles confirmed to have gram positive bacteria by Gram stain at two clinical sites within the U.S. and testing was conducted at three sites (2 external, 1 internal).

A total of 247 clinical (64 fresh and 183 seeded) and 75 challenge isolates from Enterococcus spp. (E. faecalis and E. faecium), and Staphylococcus aureus were tested to evaluate the PBC Separator with Selux AST System performance for six antimicrobials and one screening test. The number of datapoints for the various antimicrobial-organisms tested varied depending on the spectrum of activity, breakpoints, and the claimed organisms (species/group) for each antimicrobial on the panel. Datapoints ranged from 100 (e.g., Daptomycin/E. faecium) to 211 (e.g., Linezolid/Enterococcus spp.). Selux AST System MIC results from PBC Separator-prepared samples were compared to the modal value of triplicate broth microdilution reference results performed at an independent reference laboratory.

Performance was determined generally based on criteria outlined in the Class II Special Controls Guidance Document: Antimicrobial Susceptibility Test (AST) Systems including essential agreement (EA), categorical agreement (CA), and categorical errors (minor, major

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and very major errors). EA was calculated as the percentage of Selux MIC results that were within plus or minus one serial two-fold dilution of the reference result. CA was calculated as the percentage of Selux interpretive results (S/SDD/I/R) that were identical to the interpretive results of the reference result. EA of evaluable results (on-scale Selux and reference results or results in which an off-scale result was at least two doubling dilutions from the on-scale result) were also calculated. Performance was considered acceptable if the EA and CA were  $\geq 90\%$ , major error rate was  $\leq 3\%$ , and very major error rate was  $\leq 2\%$ .

A high-level summary of the PBC Separator with Selux AST System performance is described below for each antimicrobial and indicated species. Complete details and results including EA, CA and error rate analyses are summarized in Table 8 and trending analyses are summarized in Table 9.

Details of the performance for each drug/organism combination are provided below.

Table 8. PBC Separator with Selux AST System Performance

|   | Tot | No. EA | EA % | Eval EA Tot | No. Eval EA | Eval EA % | No. CA | CA % | No. R or NS | No. S | min | maj | vmj  |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
|  Ampicillin - Enterococci [Breakpoints (μg/mL): 8 (S), 16 (R)]  |   |   |   |   |   |   |   |   |   |   |   |   |   |
|  Challenge Seeded | 50 | 50 | 100 | 0 | 0 | NA | 50 | 100 | 23 | 27 | 0 | 0 | 0  |
|  Fresh | 18 | 18 | 100 | 0 | 0 | NA | 18 | 100 | 5 | 13 | 0 | 0 | 0  |
|  Clinical Seeded | 142 | 141 | 99.3 | 4 | 3 | 75 | 142 | 100 | 64 | 78 | 0 | 0 | 0  |
|  Combined | 210 | 209 | 99.52 | 4 | 3 | 75 | 210 | 100 | 92 | 118 | 0 | 0 | 0  |
|  Ceftaroline - Staphylococcus aureus [Breakpoints (μg/mL): 1 (S), 2-4 (SDD), 8 (R)]  |   |   |   |   |   |   |   |   |   |   |   |   |   |
|  Challenge Seeded | 25 | 25 | 100 | 19 | 19 | 100 | 21 | 84 | 0 | 24 | 4 | 0 | 0  |
|  Fresh | 46 | 46 | 100 | 21 | 21 | 100 | 46 | 100 | 0 | 46 | 0 | 0 | 0  |
|  Clinical Seeded | 40 | 39 | 97.5 | 15 | 14 | 93.33 | 38 | 95 | 0 | 39 | 2 | 0 | 0  |
|  Combined | 111 | 110 | 99.1 | 55 | 54 | 98.18 | 105 | 94.59 | 0 | 109 | 6 | 0 | 0  |
|  Daptomycin - Enterococcus faecalis [Breakpoints (μg/mL): 2 (S), 4 (I), 8 (R)]  |   |   |   |   |   |   |   |   |   |   |   |   |   |
|  Challenge Seeded | 25 | 24 | 96 | 1 | 0 | 0 | 24 | 96 | 0 | 25 | 0 | 1 | 0  |
|  Fresh | 13 | 13 | 100 | 3 | 3 | 100 | 13 | 100 | 0 | 13 | 0 | 0 | 0  |
|  Clinical Seeded | 65 | 63 | 96.92 | 10 | 8 | 80 | 63 | 96.92 | 0 | 65 | 1 | 1 | 0  |
|  Combined | 103 | 100 | 97.09 | 14 | 11 | 78.57 | 100 | 97.09 | 0 | 103 | 1 | 2 | 0  |
|  Daptomycin - Enterococcus faecium [Breakpoints (μg/mL): 4 (SDD), 8 (R)]  |   |   |   |   |   |   |   |   |   |   |   |   |   |
|  Challenge Seeded | 23 | 20 | 86.96 | 5 | 2 | 40 | 22 | 95.65 | 0 | 23 | 0 | 1 | 0  |
|  Fresh | 4 | 3 | 75 | 1 | 0 | 0 | 3 | 75 | 0 | 4 | 0 | 1 | 0  |
|  Clinical Seeded | 73 | 71 | 97.26 | 18 | 16 | 88.89 | 73 | 100 | 0 | 73 | 0 | 0 | 0  |
|  Combined | 100 | 94 | 94 | 24 | 18 | 75 | 98 | 98 | 0 | 100 | 0 | 2 | 0  |
|  Daptomycin - Staphylococcus aureus [Breakpoints (μg/mL): 1 (S)]  |   |   |   |   |   |   |   |   |   |   |   |   |   |
|  Challenge Seeded | 25 | 25 | 100 | 0 | 0 | NA | 25 | 100 | 0 | 25 | 0 | 0 | 0  |
|  Fresh | 46 | 46 | 100 | 0 | 0 | NA | 46 | 100 | 0 | 46 | 0 | 0 | 0  |
|  Clinical Seeded | 37 | 37 | 100 | 0 | 0 | NA | 37 | 100 | 0 | 37 | 0 | 0 | 0  |
|  Combined | 108 | 108 | 100 | 0 | 0 | NA | 108 | 100 | 0 | 108 | 0 | 0 | 0  |

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|   | Tot | No. EA | EA % | Eval EA Tot | No. Eval EA | Eval EA % | No. CA | CA % | No. R or NS | No. S | min | maj | vmj  |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
|  Linezolid – Enterococci [Breakpoints (μg/mL): 2 (S), 4 (I), 8 (R)]  |   |   |   |   |   |   |   |   |   |   |   |   |   |
|  Challenge Seeded | 50 | 50 | 100 | 47 | 47 | 100 | 50 | 100 | 0 | 50 | 0 | 0 | 0  |
|  Fresh | 18 | 17 | 94.44 | 18 | 17 | 94.44 | 17 | 94.44 | 0 | 18 | 0 | 1 | 0  |
|  Clinical Seeded | 143 | 143 | 100 | 128 | 128 | 100 | 143 | 100 | 0 | 143 | 0 | 0 | 0  |
|  Combined | 211 | 210 | 99.53 | 193 | 192 | 99.48 | 210 | 99.53 | 0 | 211 | 0 | 1 | 0  |
|  Linezolid – Staphylococcus aureus [Breakpoints (μg/mL): 4 (S), 8 (R)]  |   |   |   |   |   |   |   |   |   |   |   |   |   |
|  Challenge Seeded | 25 | 25 | 100 | 3 | 3 | 100 | 25 | 100 | 2 | 23 | 0 | 0 | 0  |
|  Fresh | 46 | 46 | 100 | 0 | 0 | NA | 46 | 100 | 0 | 46 | 0 | 0 | 0  |
|  Clinical Seeded | 37 | 37 | 100 | 1 | 1 | 100 | 36 | 97.3 | 1 | 36 | 0 | 0 | 1  |
|  Combined | 108 | 108 | 100 | 4 | 4 | 100 | 107 | 99.07 | 3 | 105 | 0 | 0 | 1  |
|  Oxacillin – Staphylococcus aureus [Breakpoints (μg/mL): 2 (S), 4 (R)]  |   |   |   |   |   |   |   |   |   |   |   |   |   |
|  Challenge Seeded | 24 | 24 | 100 | 0 | 0 | NA | 24 | 100 | 18 | 6 | 0 | 0 | 0  |
|  Fresh | 45 | 45 | 100 | 3 | 3 | 100 | 45 | 100 | 21 | 24 | 0 | 0 | 0  |
|  Clinical Seeded | 38 | 38 | 100 | 1 | 1 | 100 | 38 | 100 | 12 | 26 | 0 | 0 | 0  |
|  Combined | 107 | 107 | 100 | 4 | 4 | 100 | 107 | 100 | 51 | 56 | 0 | 0 | 0  |
|  Vancomycin – Enterococci [Breakpoints (μg/mL): 4 (S), 8-16 (I), 32 (R)]  |   |   |   |   |   |   |   |   |   |   |   |   |   |
|  Challenge Seeded | 50 | 49 | 98 | 16 | 15 | 93.75 | 50 | 100 | 20 | 30 | 0 | 0 | 0  |
|  Fresh | 18 | 17 | 94.44 | 1 | 0 | 0 | 17 | 94.44 | 5 | 13 | 1 | 0 | 0  |
|  Clinical Seeded | 141 | 132 | 93.62 | 21 | 12 | 57.14 | 135 | 95.74 | 45 | 96 | 3 | 3 | 0  |
|  Combined | 209 | 198 | 94.74 | 38 | 27 | 71.05 | 202 | 96.65 | 70 | 139 | 4 | 3 | 0  |
|  Vancomycin – Staphylococcus aureus [Breakpoints (μg/mL): 2 (S), 4-8 (I), 16 (R)]  |   |   |   |   |   |   |   |   |   |   |   |   |   |
|  Challenge Seeded | 24 | 24 | 100 | 5 | 5 | 100 | 24 | 100 | 0 | 24 | 0 | 0 | 0  |
|  Fresh | 45 | 45 | 100 | 10 | 10 | 100 | 45 | 100 | 0 | 45 | 0 | 0 | 0  |
|  Clinical Seeded | 36 | 36 | 100 | 2 | 2 | 100 | 36 | 100 | 0 | 36 | 0 | 0 | 0  |
|  Combined | 105 | 105 | 100 | 17 | 17 | 100 | 105 | 100 | 0 | 105 | 0 | 0 | 0  |

## Ampicillin

A total of 210 Enterococcus spp. (105 E. faecalis and 105 E. faecium) isolates were evaluated with ampicillin. The combined results from clinical and challenge isolate testing demonstrated an EA of 99.5% and CA of 100%, which is acceptable. There were no minor, major or very major errors. Overall, performance is acceptable. A limitation statement is included in the device labeling to address the lack of testing resistant E. faecalis.

## Cefoxitin Screen

A total of 109 S. aureus isolates were evaluated with the cefoxitin screen. The combined results from clinical and challenge isolate testing demonstrated an CA of 100%, which is acceptable. There were no minor, major or very major errors. Overall, performance is acceptable.

## Ceftaroline

A total of 111 S. aureus isolates were evaluated with the ceftaroline. The combined results from clinical and challenge isolate testing demonstrated an EA of 99.1% and CA of 94.6%, which is

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acceptable. There were six minor errors, and no major or very major errors. Overall, performance is acceptable. A limitation statement is included in the device labeling to address the lack of testing with resistant S. aureus isolates.

## Daptomycin

A total of 103 E. faecalis isolates were evaluated with daptomycin. The combined results from clinical and challenge isolate testing demonstrated an EA of 97.1% and CA of 97.1%, which is acceptable. There was one minor error, two major errors (2/100 = 2.0%) and no very major errors. Overall, performance is acceptable. A limitation statement is included in the device labeling to address the lack of testing with resistant E. faecalis isolates.

A total of 100 E. faecium isolates were evaluated with daptomycin. The combined results from clinical and challenge isolate testing demonstrated an EA of 94.0% and CA of 98.0%, which is acceptable. There were two major errors (2/100 = 2.0%) and no very major errors. Since this represents a unique case where there is no defined susceptible interpretive category (S), the susceptible-dose dependent (SDD) category is treated as an S for performance analysis. Due to the lack of an intermediate interpretive category, further analysis of the errors was performed, and adjustments were made by considering the MIC values of the errors compared to the reference MIC value. None of the major errors had an MIC value that was in essential agreement with the reference MIC value. Therefore, the adjusted major error rate is 2% (2/100). Overall, performance is acceptable. A limitation statement is included in the device labeling to address the lack of testing with resistant E. faecium isolates.

A total of 108 S. aureus isolates were evaluated with the daptomycin. The combined results from clinical and challenge isolate testing demonstrated an EA of 100% and CA of 100%, which is acceptable. There were no potential major or very major errors. Overall, performance is acceptable. A limitation statement is included in the device labeling to address the lack of testing with non-susceptible S. aureus isolates.

## Linezolid

A total of 108 S. aureus isolates were evaluated with linezolid. The combined results from clinical and challenge isolate testing demonstrated an EA of 100% and CA of 99.1%, which is acceptable. There were no major errors and one very major error (1/3 = 33.3%). Due to the lack of an intermediate interpretive category, further analysis of the errors was performed, and adjustments were made by considering the MIC values of the errors compared to the reference MIC value. The one very major error had an MIC value that was in essential agreement with the reference MIC value. Therefore, the adjusted very major error rate is 0% (0/1), which is acceptable.

A total of 211 Enterococcus spp. (105 E. faecalis and 106 E. faecium) isolates were evaluated with linezolid. The combined results from clinical and challenge isolate testing demonstrated an EA of 99.5% and CA of 99.5%, which is acceptable. There were no minor errors, one major error (1/211 = 0.5%) and no very major errors. Overall, performance is acceptable. A limitation statement is included in the device labeling to address the lack of testing with resistant Enterococcus spp. isolates.

## Oxacillin

A total of 107 S. aureus isolates were evaluated with oxacillin. The combined results from clinical and challenge isolate testing demonstrated an EA of 100% and CA of 100%, which is

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acceptable. There were no minor, major or very major errors. Overall, performance is acceptable.

# Vancomycin

A total of 209 Enterococcus spp. (103 E. faecalis and 106 E. faecium) isolates were evaluated with vancomycin. The combined results from clinical and challenge isolate testing demonstrated an EA of  $94.7\%$  and CA of  $96.7\%$ , which is acceptable. There were four minor errors, three major errors  $(3/139 = 2.2\%)$  and no very major errors. Overall, performance is acceptable.

A total of 105 S. aureus isolates were evaluated with vancomycin. The combined results from clinical and challenge isolate testing demonstrated an EA of  $100\%$  and CA of  $100\%$ , which is acceptable. There were no minor, major or very major errors. Overall, performance is acceptable. A limitation statement is included in the device labeling to address the lack of testing with resistant S. aureus isolates.

# Trending Analysis

A trending analysis was conducted using the combined data (fresh, clinical seeded, and challenge seeded) to evaluate antimicrobial-organism combinations for which Selux MIC results were determined to be one or more doubling dilutions lower or higher than the reference result (Table 9). MIC results that were off-scale for both the reference and Selux were not considered in the trending analysis. Antimicrobial-organism combinations for which the difference between the percentage of isolates with higher or lower MIC values was  $\geq 30\%$  with a statistically significant confidence interval were considered to have evidence of trending and are addressed in the labeling.

Table 9. PBC Separator with Selux AST System Performance - Trending

|  Abx | Organism Name | Total On Scale for Trending | >=1 Dilution Lower # (%) | Exact # | >=1 Dilution Higher # (%) | Percent Difference (95% CI) | Significant Trending Noted  |
| --- | --- | --- | --- | --- | --- | --- | --- |
|  Ampicillin | Enterococcus faecalis | 0 | 0 (0) | 0 | 0 (0) | 0 | NA  |
|  Ampicillin | Enterococcus faecium | 11 | 4 (36.36) | 2 | 5 (45.45) | 9% (-28%, 43%) | No  |
|  Ceftaroline | Staphylococcus aureus | 71 | 6 (8.45) | 18 | 47 (66.2) | 58% (43%, 69%) | Yes  |
|  Daptomycin | Enterococcus faecalis | 30 | 16 (53.33) | 0 | 14 (46.67) | -7% (-30%, 18%) | No  |
|  Daptomycin | Enterococcus faecium | 56 | 36 (64.29) | 6 | 14 (25) | -39% (-54%, -21%) | Yes  |
|  Daptomycin | Staphylococcus aureus | 32 | 32 (100) | 0 | 0 (0) | -100% (-100%, -85%) | Yes  |
|  Linezolid | Enterococcus faecalis | 105 | 44 (41.9) | 56 | 5 (4.76) | -37% (-47%, -26%) | Yes  |
|  Linezolid | Enterococcus faecium | 106 | 41 (38.68) | 50 | 15 (14.15) | -25% (-35%, -13%) | No  |
|  Linezolid | Staphylococcus aureus | 39 | 36 (92.31) | 3 | 0 (0) | -92% (-97%, -77%) | Yes  |
|  Oxacillin | Staphylococcus aureus | 21 | 6 (28.57) | 3 | 12 (57.14) | 29% (-1%, 52%) | No  |
|  Vancomycin | Enterococcus faecalis | 39 | 6 (15.38) | 5 | 28 (71.79) | 56% (35%, 71%) | Yes  |
|  Vancomycin | Enterococcus faecium | 5 | 3 (60) | 0 | 2 (40) | -20% (-60%, 32%) | No  |

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|  Abx | Organism Name | Total On Scale for Trending | >= 1 Dilution Lower # (%) | Exact # | >= 1 Dilution Higher # (%) | Percent Difference (95% CI) | Significant Trending Noted  |
| --- | --- | --- | --- | --- | --- | --- | --- |
|  Vancomycin | Staphylococcus aureus | 58 | 14 (24.14) | 17 | 27 (46.55) | 22% (5%, 38%) | No  |

Analysis of trending indicated that PBC Separator with Selux AST System MIC values for certain antimicrobial/organism combinations tended to be at least one doubling dilution lower than the reference MIC value. The following statement is included as a footnote to the AST performance table: PBC Separator with Selux AST System MIC values for the following antimicrobial/organism combinations tended to be at least one doubling dilution lower than the reference MIC value:

- Daptomycin: E. faecium, S. aureus
- Linezolid: E. faecalis, S. aureus

Analysis of trending indicated that PBC Separator with Selux AST System MIC values for certain antimicrobial/organism combinations tended to be at least one doubling dilution higher than the reference MIC value. The following statement is included as a footnote to the AST performance table: PBC Separator with Selux AST System MIC values for the following antimicrobial/organism combinations tended to be at least one doubling dilution higher than the reference MIC value:

- Ceftaroline: S. aureus
- Vancomycin: E. faecalis

2. Matrix Comparison:
Not applicable.

Clinical Studies:

1. Clinical Sensitivity:
Not applicable.

2. Clinical Specificity:
Not applicable.

3. Other Clinical Supportive Data (When 1. and 2. Are Not Applicable):
Not applicable.

Clinical Cut-Off:
Not applicable.

Expected Values/Reference Range:
The FDA-recognized/approved susceptibility interpretive criteria for the antimicrobials evaluated with the PBC Separator and Selux AST System are listed in Table 10 below.

Table 10. Reportable MIC Ranges and Organism-Specific Breakpoints for Antimicrobials Tested with the PBC Separator with Selux AST System.

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|  Antimicrobial | Indicated Organism Group | Selux AST System Reportable Range (μg/mL) | FDA-Recognized/Approved Breakpoints* (μg/mL)  |   |   |   |
| --- | --- | --- | --- | --- | --- | --- |
|   |   |   |  S | SDD | I | R  |
|  Ampicillin | Enterococci | ≤2 to ≥64 | ≤8 | - | - | ≥16  |
|  Ceftaroline | Staphylococcus aureus | ≤0.25 to ≥16 | ≤1 | 2-4 | - | ≥8  |
|  Daptomycin | Enterococcus faecium | 1 to ≥32 | - | ≤4 | - | ≥8  |
|   |  Enterococcus faecalis | ≤1 to ≥32 | ≤2 | - | 4 | ≥8  |
|   |  Staphylococcus aureus | ≤0.25 to ≥8 | ≤1 | - | - | -  |
|  Linezolid | Enterococci | ≤0.5 to ≥16 | ≤2 | - | 4 | ≥8  |
|   |  Staphylococcus aureus | ≤1 to ≥32 | ≤4 | - | - | ≥8  |
|  Oxacillin | Staphylococcus aureus | ≤0.5 to ≥16 | ≤2 | - | - | ≥4  |
|  Vancomycin | Enterococci | ≤1 to ≥64 | ≤4 | - | 8-16 | ≥32  |
|   |  Staphylococcus aureus | ≤0.5 to ≥32 | ≤2 | - | 4-8 | ≥16  |
|  Cefoxitin Screen (mecA oxacillin resistance) | Staphylococcus aureus | SN or SP | NA | NA | NA | NA  |

S, Susceptible; SDD, Susceptible-Dose Dependent I, Intermediate; R, Resistant; (-) Indicates that a corresponding MIC is not defined for that category; NA: FDA breakpoints not applicable because Cefoxitin Screen is a qualitative test based on an MIC value of 4 μg/mL with results reported either as SN (screen negative) or SP (screen positive).
* FDA STIC Website https://www.fda.gov/drugs/development-resources/fda-recognized-antimicrobial-susceptibility-test-interpretive-criteria.

## F Other Supportive Performance Characteristics Data:

## Blood Culture Bottle Compatibility Analytical Study

Eleven types of blood culture bottles incubated in BD BACTEC and bioMérieux BacT/ALERT VIRTUO continuous monitoring blood culture systems were evaluated with the PBC Separator with Selux AST System. Bacterial samples were seeded at clinically relevant concentrations into the blood culture bottles with the manufacturer recommended volume of human blood and loaded into a continuous monitoring blood culture system and incubated until positivity. Positive blood culture samples were then processed with the PBC Separator with Selux AST System. One isolate from each reporting group was tested with 3 replicates per bottle type and evaluated with all claimed antimicrobials. Aerobic and anaerobic bottles were seeded with *E. faecalis* and *S. aureus*.

Selux AST System MIC results from tested bottle types were compared to modal BMD reference results, with an EA ≥ 90% being deemed acceptable. Performance results are summarized in Table 11 for all bottle types and presented separately for BD BACTEC (Tables 12 and 13) and bioMérieux BacT/ALERT bottles (Tables 14 and 15), respectively. All drug-organism combinations demonstrated EA ≥ 90% for each blood bottle type. The following exceptions were noted:

- Cefoxitin Screen was considered separately since results are qualitative-only (positive or negative). Cefoxitin-Staphylococci demonstrated 66.7% (2/3) out-of-agreement results in BD BACTEC Aerobic Plus bottles. However, the clinical data included MIC results from this drug-organism in this bottle type with 100% (26/26) agreement. Given the totality of data, overall performance is considered acceptable.
- Oxacillin-Staphylococci demonstrated a CA of 66.7% (2/3) in BD BACTEC Aerobic Plus bottles although EA was 100.0% (3/3). However, the clinical data included MIC results from this drug-organism in this bottle type with 100% (26/26) agreement. Given the totality of data, overall performance is considered acceptable.

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- Vancomycin-Enterococci demonstrated an EA of  $66.7\%$  (2/3) in BD BACTEC Anaerobic Plus bottles resulting in a combined EA of  $83.3\%$  (5/6). However, the clinical data included MIC results from this drug-organism in this bottle type with  $100\%$  (7/7) agreement. Based on the totality of data, the performance is acceptable.

Table 11. Performance Summary of Blood Culture Bottles and Systems

|  Continuous Monitoring System | Blood Culture Bottle | Fill Volume | # EA/ Total | % EA | # CA/ Total | % CA  |
| --- | --- | --- | --- | --- | --- | --- |
|  BD BACTEC | Plus Aerobic | 8-10 mL | 29/30 | 96.7 | 28/30 | 93.3  |
|   |  Plus Anaerobic | 8-10 mL | 29/30 | 96.7 | 29/30 | 96.7  |
|   |  Standard Aerobic | 8-10 mL | 30/30 | 100 | 30/30 | 100  |
|   |  Standard Anaerobic | 5-7 mL | 30/30 | 100 | 30/30 | 100  |
|   |  Lytic Anaerobic | 8-10 mL | 30/30 | 100 | 30/30 | 100  |
|   |  Peds Plus | 1-3 mL | 30/30 | 100 | 30/30 | 100  |
|  bioMérieux BACT/ALERT VIRTUO | FA Plus (resin aerobic) | 8-10 mL | 30/30 | 100 | 30/30 | 100  |
|   |  FN Plus (resin anaerobic) | 8-10 mL | 30/30 | 100 | 30/30 | 100  |
|   |  SA (standard aerobic) | 8-10 mL | 30/30 | 100 | 30/30 | 100  |
|   |  SN (standard anaerobic) | 8-10 mL | 30/30 | 100 | 30/30 | 100  |
|   |  PF Plus (pediatric resin aerobic) | 8-10 mL | 30/30 | 100 | 30/30 | 100  |

Table 12. PBC Separator Performance with BD BACTEC Aerobic Bottles

|  Antimicrobial | Indicated Organism(s) | Standard Aerobic |   | Aerobic Plus |   | Peds Plus  |   |
| --- | --- | --- | --- | --- | --- | --- | --- |
|   |   |  # EA / Total | % EA | # EA / Total | % EA | # EA / Total | % EA  |
|  Ampicillin | Enterococcus faecalis | 3/3 | 100 | 3/3 | 100 | 3/3 | 100  |
|  Ceftaroline | Staphylococcus aureus | 3/3 | 100 | 3/3 | 100 | 3/3 | 100  |
|  Daptomycin | Enterococcus faecalis | 3/3 | 100 | 3/3 | 100 | 3/3 | 100  |
|   |  Staphylococcus aureus | 3/3 | 100 | 3/3 | 100 | 3/3 | 100  |
|   |  Total | 6/6 | 100 | 6/6 | 100 | 6/6 | 100  |
|  Linezolid | Enterococcus faecalis | 3/3 | 100 | 3/3 | 100 | 3/3 | 100  |
|   |  Staphylococcus aureus | 3/3 | 100 | 3/3 | 100 | 3/3 | 100  |
|   |  Total | 6/6 | 100 | 6/6 | 100 | 6/6 | 100  |
|  Oxacillin | Staphylococcus aureus | 3/3 | 100 | 3/3 | 100 | 3/3 | 100  |
|  Vancomycin | Enterococcus faecalis | 3/3 | 100 | 3/3 | 100 | 3/3 | 100  |
|   |  Staphylococcus aureus | 3/3 | 100 | 3/3 | 100 | 3/3 | 100  |
|   |  Total | 6/6 | 100 | 6/6 | 100 | 6/6 | 100  |

Table 13. PBC Separator Performance with BD BACTEC Anaerobic Bottles

|  Antimicrobial | Indicated Organism(s) | Standard Anaerobic |   | Anaerobic Plus |   | Lytic Anaerobic  |   |
| --- | --- | --- | --- | --- | --- | --- | --- |
|   |   |  # EA / Total | % EA | # EA / Total | % EA | # EA / Total | % EA  |
|  Ampicillin | Enterococcus faecalis | 3/3 | 100 | 3/3 | 100 | 3/3 | 100  |
|  Ceftaroline | Staphylococcus aureus | 3/3 | 100 | 3/3 | 100 | 3/3 | 100  |
|  Daptomycin | Enterococcus faecalis | 3/3 | 100 | 3/3 | 100 | 3/3 | 100  |
|   |  Staphylococcus aureus | 3/3 | 100 | 3/3 | 100 | 3/3 | 100  |
|   |  Total | 6/6 | 100 | 6/6 | 100 | 6/6 | 100  |
|  Linezolid | Enterococcus faecalis | 3/3 | 100 | 3/3 | 100 | 3/3 | 100  |

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|  Antimicrobial | Indicated Organism(s) | Standard Anaerobic |   | Anaerobic Plus |   | Lytic Anaerobic  |   |
| --- | --- | --- | --- | --- | --- | --- | --- |
|   |   |  # EA / Total | % EA | # EA / Total | % EA | # EA / Total | % EA  |
|   | Staphylococcus aureus | 3/3 | 100 | 3/3 | 100 | 3/3 | 100  |
|   |  Total | 6/6 | 100 | 6/6 | 100 | 6/6 | 100  |
|  Oxacillin | Staphylococcus aureus | 3/3 | 100 | 3/3 | 100 | 3/3 | 100  |
|  Vancomycin | Enterococcus faecalis | 3/3 | 100 | 2/3 | 66.7 | 3/3 | 100  |
|   |  Staphylococcus aureus | 3/3 | 100 | 3/3 | 100 | 3/3 | 100  |
|   |  Total | 6/6 | 100 | 5/6 | 83.3 | 6/6 | 100  |

Table 14. PBC Separator Performance with bioMérieux BacT/ALERT Aerobic Bottles

|  Antimicrobial | Indicated Organism(s) | SA |   | FA Plus |   | PF Plus  |   |
| --- | --- | --- | --- | --- | --- | --- | --- |
|   |   |  # EA / Total | % EA | # EA / Total | % EA | # EA / Total | % EA  |
|  Ampicillin | Enterococcus faecalis | 3/3 | 100 | 3/3 | 100 | 3/3 | 100  |
|  Ceftaroline | Staphylococcus aureus | 3/3 | 100 | 3/3 | 100 | 3/3 | 100  |
|  Daptomycin | Enterococcus faecalis | 3/3 | 100 | 3/3 | 100 | 3/3 | 100  |
|   |  Staphylococcus aureus | 3/3 | 100 | 3/3 | 100 | 3/3 | 100  |
|   |  Total | 6/6 | 100 | 6/6 | 100 | 6/6 | 100  |
|  Linezolid | Enterococcus faecalis | 3/3 | 100 | 3/3 | 100 | 3/3 | 100  |
|   |  Staphylococcus aureus | 3/3 | 100 | 3/3 | 100 | 3/3 | 100  |
|   |  Total | 6/6 | 100 | 6/6 | 100 | 6/6 | 100  |
|  Oxacillin | Staphylococcus aureus | 3/3 | 100 | 3/3 | 100 | 3/3 | 100  |
|  Vancomycin | Enterococcus faecalis | 3/3 | 100 | 3/3 | 100 | 3/3 | 100  |
|   |  Staphylococcus aureus | 3/3 | 100 | 3/3 | 100 | 3/3 | 100  |
|   |  Total | 6/6 | 100 | 6/6 | 100 | 6/6 | 100  |

Table 15. PBC Separator Performance with bioMérieux BacT/ALERT Anaerobic Bottles

|  Antimicrobial | Indicated Organism(s) | SN |   | FN Plus  |   |
| --- | --- | --- | --- | --- | --- |
|   |   |  # EA / Total | % EA | # EA / Total | % EA  |
|  Ampicillin | Enterococcus faecalis | 3/3 | 100 | 3/3 | 100  |
|  Ceftaroline | Staphylococcus aureus | 3/3 | 100 | 3/3 | 100  |
|  Daptomycin | Enterococcus faecalis | 3/3 | 100 | 3/3 | 100  |
|   |  Staphylococcus aureus | 3/3 | 100 | 3/3 | 100  |
|   |  Total | 6/6 | 100 | 6/6 | 100  |
|  Linezolid | Enterococcus faecalis | 3/3 | 100 | 3/3 | 100  |
|   |  Staphylococcus aureus | 3/3 | 100 | 3/3 | 100  |
|   |  Total | 6/6 | 100 | 6/6 | 100  |
|  Oxacillin | Staphylococcus aureus | 3/3 | 100 | 3/3 | 100  |
|  Vancomycin | Enterococcus faecalis | 3/3 | 100 | 3/3 | 100  |
|   |  Staphylococcus aureus | 3/3 | 100 | 3/3 | 100  |
|   |  Total | 6/6 | 100 | 6/6 | 100  |

VIII Proposed Labeling:

The labeling supports the finding of substantial equivalence for this device.

IX Conclusion:

The submitted information in this premarket notification is complete and supports a substantial equivalence decision.

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To support the implementation of changes to FDA-recognized susceptibility test interpretive criteria (i.e., breakpoints), this submission incorporated by reference a breakpoint change protocol that was reviewed and accepted by FDA in submission K211759. This protocol addresses future revisions to device labeling in response to breakpoint changes that are recognized on the FDA STIC webpage (https://www.fda.gov/Drugs/DevelopmentApprovalProcess/DevelopmentResources/ucm410971.htm). The protocol outlined the specific procedures and acceptance criteria that Selux intends to use to evaluate the Selux AST System when revised breakpoints for indicated drugs are published on the FDA STIC webpage. The breakpoint change protocol included with the submission indicated that if specific criteria are met, Selux will update the Selux AST System label to include (1) the new breakpoints, (2) an updated performance section after re-evaluation of data in this premarket notification with the new breakpoints, and (3) any new limitations as determined by their evaluation.

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---

**Source:** [https://fda.innolitics.com/submissions/MI/subpart-b%E2%80%94diagnostic-devices/QZX/K244044](https://fda.innolitics.com/submissions/MI/subpart-b%E2%80%94diagnostic-devices/QZX/K244044)

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