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 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 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

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 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, Morganii, Proteus mirabilis, Proteus vulgaris, Serratia marcescens, Pseudomonas aeruginosa

Tobramycin: Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa

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.

Device Description

The Positive Blood Culture (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 a tuned McFarland-equivalent inoculum from positive blood culture bottles that have rung positive on a continuous monitoring blood culture system. Inoculums containing monomicrobial, gram negative bacteria are used for AST processing with the Selux AST System. The Selux AST System includes a sample prep station (i.e., AST Workbench), an Inoculator, an Analyzer, Workbench Computer, 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. The PBC Separator contains embedded software and a graphical user interface that guides users through the PBC Separator workflow. Once processing of the PBC sample is complete, the user transfers the tuned McFarland inoculum to the Selux AST System for further AST processing.

The PBC Separator with Selux AST System can only provide AST results for monomicrobial samples. Since the PBC Separator with Selux AST System do not perform identification (ID), the monomicrobial nature of the sample under test must be confirmed by an FDA-cleared direct-frompositive blood culture ID system.

While PBC Separator processing can be performed without species-level ID, this information is required for the Selux AST System to interpret and report susceptibility results. 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) at any time, once the sample ID is entered into the LIS.

The PBC Separator with the Selux AST System utilizes the Selux Gram Negative Panel, a 384well panel that provides parallel results for the antimicrobials indicated for each sample type. The Selux AST System software masks non-indicated results. The average time-to-result for positive blood culture processed with the PBC Separator and Selux AST System is under 7 hours.

AI/ML Overview

Here's a breakdown of the acceptance criteria and study details for the PBC Separator with Selux AST System, based on the provided FDA 510(k) summary:

Acceptance Criteria and Device Performance

The core performance criteria for the PBC Separator with Selux AST System relate to its ability to accurately determine antimicrobial susceptibility. The primary metric used is Essential Agreement (EA), which measures how closely the MIC results from the device match the reference method, and Category Agreement (CA), which assesses agreement in susceptibility interpretations (Susceptible, Intermediate, Resistant - SIR).

Overall Acceptance Criterion: The device must meet performance criteria for each indication, generally interpreted as high percentages of Essential Agreement (EA) and Category Agreement (CA) (typically >90% as seen in the tables for acceptable overall performance, though individual instances below 90% might be deemed acceptable based on the totality of data).

1. Table of Acceptance Criteria and the Reported Device Performance

Performance Metric	Acceptance Criterion (Implicit)	Reported Device Performance (Summary)	Notes
Intra-Site Reproducibility	≥ 95% Best- and Worst-Case	≥ 95% Best- and Worst-Case for all tested antimicrobials (Min. 98.1%)	Achieved for all antimicrobials
Inter-Site Reproducibility	> 95% Best- and Worst-Case	> 95% Best- and Worst-Case for all tested antimicrobials (Min. 95.8%)	Achieved for all antimicrobials
Post-Positivity Sample Stability (16 hr)	> 95% Essential Agreement	99.6% (264/265 results in EA)	Achieved overall; individual antimicrobial EA >95%
Blood Culture Bottle Compatibility (Aerobic)	> 89.9% Essential Agreement for all tested bottle types	99.3% overall EA (1629/1640); each aerobic bottle type ≥ 98.5% EA	Except for one case (Ciprofloxacin/Enterobacterales in bioMérieux BacT/ALERT SA) which was 89.3%, but deemed acceptable.
Blood Culture Bottle Compatibility (Anaerobic)	> 89.9% Essential Agreement for all tested bottle types	99.5% overall EA (974/979); each anaerobic bottle type ≥ 98.5% EA	Except for a few cases below 90% (Ciprofloxacin/Enterobacterales in BD BACTEC Lytic Anaerobic (85.7%) and bioMerieux BacT/ALERT FN Plus (92.3%); Ampicillin-Sulbactam/Enterobacterales in BD BACTEC Lytic Anaerobic (92.9%)), but deemed acceptable.
Endogenous Interferents (MIC EA)	> 89.9% Essential Agreement for every interferent	> 89.9% Essential Agreement for every interferent tested (most combinations were 100%)	Except for Piperacillin-Tazobactam with K. pneumoniae in all endogenous interferents, which showed <90% EA and very major errors, and Tobramycin with P. aeruginosa (80-92.9%), which were noted as having less than 90% EA but deemed acceptable.
Exogenous Interferents (MIC EA)	> 89.9% Essential Agreement for every interferent	> 89.9% Essential Agreement for every interferent tested (most combinations were 100%)	Except for Cefepime/Enterobacterales, Imipenem/Enterobacterales, Minocycline/Enterobacterales (with some interferents), Piperacillin-Tazobactam with K. pneumoniae in all exogenous interferents (<90% EA and very major errors), and Tobramycin/Enterobacterales with Cefpodoxime (77.8%), flagged as having less than 90% EA but deemed acceptable.
Carry-Over/Cross-Contamination	> 89.9% Essential Agreement	100% for E. coli (60/60); 98.2% for K. pneumoniae (54/55). No contamination on purity plates.	Achieved.
Clinical Performance (EA)	Generally high percentage agreement, individual variations noted.	Varied by antimicrobial-organism combination (e.g., Amikacin/A. baumannii (complex): 92.1% EA; Ceftazidime/P. aeruginosa: 100% EA)	Performance demonstrated for all combinations although some EA values were below 90% in the "Total Eval" category (e.g. Amikacin/Enterobacterales: 66.7%).
Clinical Performance (CA)	Generally high percentage agreement.	Varied by antimicrobial-organism combination (e.g., Amikacin/A. baumannii (complex): 94.7% CA; Ceftazidime/P. aeruginosa: 100% CA)	Some EA values were below 90% in the "Total Eval" category which might have an impact on the CA, although not explicit in the table.
QC Testing	95% performance criteria	Met for all antimicrobials	Achieved.

Study Details

The document primarily describes analytical and clinical studies for the performance evaluation of the PBC Separator with Selux AST System.

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

Reproducibility:
- Intra-site: Minimum of 45 results per antimicrobial (5 samples * 3 triplicates * 3 days).
- Inter-site: Minimum of 135 results per antimicrobial (5 samples * 3 triplicates * 3 days * 3 sites).
- Data Provenance: Not explicitly stated as retrospective or prospective, but involves seeding isolates into fresh human blood and processing, suggesting a controlled laboratory setting. The "3 sites (2 external, 1 internal)" suggests internal and possibly US/international external sites.
Post-Positivity Sample Stability: 265 results comparing 16-hour processing to 0-hour processing.
- Data Provenance: Fresh human blood from a healthy donor.
Blood Culture Bottle Compatibility:
- Aerobic: 1640 results across 11 bottle types.
- Anaerobic: 979 results across 11 bottle types.
- Data Provenance: Seeded bacterial samples at clinically relevant concentrations into blood culture bottles with manufacturer-recommended volumes of healthy donor human blood.
Interfering Substances Testing:
- Each interferent tested involved "at least one species for each reporting group for each antimicrobial."
- Data Provenance: Healthy donor blood used to seed interferents and bacteria.
Carry-Over/Cross-Contamination Study: 5 E. coli and 5 K. pneumoniae positive blood culture samples; 5 AST panels for each organism.
- Data Provenance: Seeded isolates.
Clinical Studies:
- Total Isolates: 469 clinical (162 fresh and 307 seeded) and 87 challenge isolates.
- Organisms: 12 Enterobacterales species, Acinetobacter baumannii complex, and Pseudomonas aeruginosa.
- Antimicrobials: 17.
- Total Data Points: Varied from 38 to 469 per antimicrobial-organism combination.
- Data Provenance:
  - Fresh clinical samples: "left over from routine clinical care" from two clinical sites in New York City. This indicates retrospective use of fresh samples collected in a clinical setting.
  - Seeded samples: "banked frozen isolates seeded... into blood culture bottles together with approximately 10 mL of fresh human blood from a healthy donor." These seeded samples were chosen "to represent geographic diversity across the continental U.S." This component is laboratory-based but designed to represent real-world diversity.

3. Number of Experts Used to Establish the Ground Truth for the Test Set and their Qualifications

The document does not explicitly state the number of experts or their qualifications for establishing ground truth. However, it indicates that triplicate broth microdilution results performed at an independent reference laboratory were used as the reference method. This implies that the ground truth was established by laboratory personnel in a CLIA-certified or equivalent reference lab, following a recognized standard for AST.

4. Adjudication Method for the Test Set

The document does not describe an explicit adjudication method (e.g., 2+1, 3+1) for the interpretation of test results or discrepancies. The comparison is made directly between the device's results and the reference broth microdilution results. Any discrepancies would be evaluated against established acceptance criteria, but no formal expert adjudication process is detailed.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was done

No, a multi-reader multi-case (MRMC) comparative effectiveness study was not done. The device is for antimicrobial susceptibility testing, which does not involve human readers interpreting images or data alongside AI. The device provides a direct microbiological result (MIC and SIR category).

6. If a Standalone Performance Study (algorithm only without human-in-the-loop performance) was done

Yes, the studies described are primarily standalone performance studies for the device. The "PBC Separator with Selux AST System" directly processes samples and generates MICs and SIR interpretations. While requiring inputs like Gram stain and organism identification before result interpretation, the AST process itself (lysis, centrifugation, optical density measurements, and MIC determination) is automated by the device without real-time human intervention in the result generation. The performance is compared to a reference standard (broth microdilution), reflecting the algorithm's output.

7. The Type of Ground Truth Used

The ground truth used for all performance evaluations (reproducibility, stability, compatibility, interferents, clinical performance) was broth microdilution (BMD), which is the gold standard reference method for antimicrobial susceptibility testing. For the clinical studies, it specifies "triplicate broth microdilution results performed at an independent reference laboratory."

8. The Sample Size for the Training Set

The document does not specify the sample size for the training set. The provided information focuses entirely on the validation and testing of the device's performance, not its development or training data.

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

Since the document does not mention a training set or its size, it also does not describe how the ground truth for a training set was established.

Summary

{0}------------------------------------------------

Image /page/0/Picture/0 description: The image contains the logo of the U.S. Food and Drug Administration (FDA). The logo consists of two parts: the Department of Health & Human Services logo on the left and the FDA logo on the right. The FDA logo features the letters 'FDA' in a blue square, followed by the words 'U.S. FOOD & DRUG ADMINISTRATION' in blue text.

July 8, 2024

Selux Diagnostics, Inc Carrene Plummer VP, Regulatory and Quality 56 Roland Street, Suite 206 Charlestown, MA, 02129

Re: K223493

Trade/Device Name: PBC Separator with Selux AST System Regulation Number: 21 CFR 866.1650 Regulation Name: A cellular analysis system for multiplexed antimicrobial susceptibility Regulatory Class: Class II Product Code: QZX, LON, LTT, LTW

Dear Carrene Plummer:

The Food and Drug Administration (FDA) is sending this letter to notify you of an administrative change related to your previous substantial equivalence (SE) determination letter dated February 15, 2024. Specifically, FDA is updating this SE Letter as an administrative correction to include all cleared drugorganism combinations in your Indications for Use.

Please note that the 510(k) submission was not re-reviewed. For questions regarding this letter please contact Patrick Axtell, Ph.D., ORP: Office of Regulatory Programs, 301-796-6462, patrick.axtell(@fda.hhs.gov.

Sincerely.

Ribhi Shawar -S

Ribhi Shawar, Ph.D. (ABMM) Branch Chief, General Bacteriology and Antimicrobial Susceptibility Branch Division of Microbiology Devices OHT7: Office of In Vitro Diagnostics Office of Product Evaluation and Quality Center for Devices and Radiological Health

{1}------------------------------------------------

Image /page/1/Picture/0 description: The image contains the logo of the U.S. Food and Drug Administration (FDA). The logo consists of two parts: the Department of Health & Human Services logo on the left and the FDA acronym with the full name of the agency on the right. The FDA part of the logo is in blue, with the acronym in a square and the full name, "U.S. Food & Drug Administration," written out next to it.

February 15, 2024

Selux Diagnostics, Inc % Carrene Plummer Senior Director, Regulatory Affairs PBO Consulting 2212 East Pratt Street Baltimore, Maryland 21231

Re: K223493

Trade/Device Name: PBC Separator Regulation Number: 21 CFR 866.1650 Regulation Name: A Cellular Analysis System For Multiplexed Antimicrobial Susceptibility Regulatory Class: Class II Product Code: OZX, LON, LTT, LTW Dated: January 23, 2024 Received: January 23, 2024

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 (the 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 available at https://www.accessdata.fda.gov/scripts/cdrb/cfdocs/cfpmn/pmn.cfm identifies combination product submissions. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.

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

Additional information about changes that may require a new premarket notification are provided in the FDA guidance documents entitled "Deciding When to Submit a 510(k) for a Change to an Existing Device" (https://www.fda.gov/media/99812/download) and "Deciding When to Submit a 510(k) for a Software Change to an Existing Device" (https://www.fda.gov/media/99785/download).

{2}------------------------------------------------

Your device is also subject to, among other requirements, the Quality System (QS) regulation (21 CFR Part 820), which includes, but is not limited to, 21 CFR 820.30. Design controls; 21 CFR 820.90. Nonconforming product; and 21 CFR 820.100, Corrective and preventive action. Please note that regardless of whether a change requires premarket review, the OS regulation requires device manufacturers to review and approve changes to device design and production (21 CFR 820.70) and document changes and approvals in the device master record (21 CFR 820.181).

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 Part 803) for devices or postmarketing safety reporting (21 CFR Part 4, Subpart B) for combination products (see https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safetyreporting-combination-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 Part 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR Parts 1000-1050.

Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR 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 -S

{3}------------------------------------------------

Indications for Use

510(k) Number (if known) K223493

Device Name PBC Separator with Selux AST System

Indications for Use (Describe)

The PBC Separator with Selux AST System is an automated inoculum preparation system that uses lysis, centrifygation 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 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. 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

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 cloacae complex, Escherichia coli, Klebsiella aerogenes, Klebsiella oxytoca, Klebsiella pneumoniae, Morganii, Proteus mirabilis, Proteus vulgaris, Serratia marcescens, Pseudomonas aeruginosa

Ceftazidime: Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa

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

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

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

Ertapenem: Citrobacter freundii complex, Cirobacter cloacae complex, Escherichia coli, Klebsiella aerogenes, Klebsiella oxytoca, Klebsiella pneumoniae, Morganii, Proteus mirabilis, Proteus vulgaris, Serratia marcescens

Gentamicin: Citrobacter freundii complex, Citrobacter cloacae complex, Escherichia coli, Klebsiella aerogenes, Klebsiella oxytoca, Klebsiella pneumoniae, 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 cloacae complex, Escherichia coli, Klebsiella oxytoca, Klebsiella pneumoniae, 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

{4}------------------------------------------------

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 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.

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

Prescription Use (Part 21 CFR 801 Subpart D)

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

CONTINUE ON A SEPARATE PAGE IF NEEDED.

This section applies only to requirements of the Paperwork Reduction Act of 1995.

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

The burden time for this collection of information is estimated to average 79 hours per response, including the time to review instructions, search existing data sources, gather and maintain the data needed and complete and review the collection of information. Send comments regarding this burden estimate or any other aspect of this information collection, including suggestions for reducing this burden, to:

Department of Health and Human Services Food and Drug Administration Office of Chief Information Officer Paperwork Reduction Act (PRA) Staff PRAStaff@fda.hhs.gov

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

{5}------------------------------------------------

510(k) Summary for the PBC Separator with Selux AST System

Date prepared: June 28, 2024

Submitter:

Selux Diagnostics, Inc. 56 Roland St Suite 106 Charlestown, MA 02129 Tel. 617-945-9383

Contact:

Carrene Plummer Tel. 520-405-1462

Subject Device

Trade Name:	PBC Separator with Selux AST System
Common Name:	Antimicrobial Susceptibility Test System
Regulation Number:	21 CFR 866.1650
Regulation Name:	Positive Blood Culture Processor For Inoculum Preparation Used for
	Antimicrobial Susceptibility Testing
Regulatory Class:	Class II
Product Code:	QZX, LON, LTT, LTW
Classification Panel:	83 (Microbiology)

Predicate Device

Trade Name:	eQUANT System
Manufacturer:	Avails Medical, Inc.
510(k) Reference:	K231536
Common Name:	eQUANT System
Regulation Number:	21 CFR 866.1650
Regulation Name:	Positive Blood Culture Identification and AST Kit
Regulatory Class:	Class II
Product Code:	QZX, JTN
Classification Panel:	83 (Microbiology)

Device Description

{6}------------------------------------------------

PBC Separator workflow. Once processing of the PBC sample is complete, the user transfers the tuned McFarland inoculum to the Selux AST System for further AST processing.

Principle of Operation

The PBC Separator automatically prepares a tuned bacterial inoculum directly from a blood culture bottle sample that "rang" positive on an FDA-cleared continuous monitoring blood culture system, including the Becton Dickinson BACTEC, the bioMerieux BacT/Alert 3D, and the bioMerieux Virtuo. The PBC Separator removes contaminants through repeated centrifugation-wash cycles and specific chemical lysis of mammalian cells and cell fragments. 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 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.

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. Organism identification (ID) is not needed to initiate testing with the Selux AST System. However, the organism ID is necessary for a result to be interpreted and reported because the MIC-determining algorithm is species-specific as is the interpretative Susceptible, Intermediate, or Resistant (SIR) determination. Any FDA-cleared method may be used to provide an ID including biochemical techniques, matrix-assisted laser desorption/isotherm mass spectrometry, and multiplex genetic assays.

Intended Use and 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.

{7}------------------------------------------------

Indications for Use

The PBC Separator with the Selux AST System is an automated inoculum preparation system that uses lysis, centrifugation and sequential optical density measurements to generate a McFarlandequivalent 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 by Gram stain. Organism identification is required for AST result interpretation and reporting, per the Selux AST System instructions for use.

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

Ampicillin: Escherichia coli, Proteus mirabilis

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

Cefazolin: Escherichia coli, Klebsiella pneumoniae

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

Meropenem: Acinetobacter baumannii complex, Citrobacter freundii complex, Citrobacter koseri, Enterobacter cloacae complex, Escherichia coli, Klebsiella oxytoca, Klebsiella

{8}------------------------------------------------

pneumoniae, Morganella morganii. Proteus mirabilis, Proteus vulgaris, Serratia marcescens, Pseudomonas aeruginosa Minocycline: Acinetobacter baumannii complex, Escherichia coli, Klebsiella pneumoniae

Tobramycin: Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa

Comparison of Technological Characteristics with the Predicate and Reference Devices

The technological characteristics of the PBC Separator are substantially equivalent to the primary predicate device, the eQUANT System (K231536) in terms of intended use, application, user population, basic design, performance, and labeling.

Device & PredicateDevices:	K223494Device	K231536Predicate
Device Trade Name	PBC Separator with Selux ASTSystem	eQUANT System
Device Characteristics	The PBC Separator with the SeluxAST System is an automatedinoculum preparation system that useslysis, centrifugation and sequentialoptical density measurements togenerate a McFarland-equivalentsuspension from positive bloodculture samples that can be used forquantitative in vitro antimicrobialsusceptibility testing by the SeluxAST System. Samples are processeddirectly from blood culture samplesidentified as positive by a continuousmonitoring blood culture system.Samples should be confirmed asmonomicrobial, gram negative rodsby Gram stain. Organismidentification is required for ASTresult interpretation and reporting, perthe Selux AST System instructions foruse.	The eQUANT™ System is anautomated inoculum preparation systemthat uses potentiometric sensing ofoxidation-reduction potential changesdue to pathogen metabolism to generatea 0.5 McFarland equivalent suspension(the eMcFarland or eMcF) from positiveblood culture samples that can be usedfor direct, qualitative in vitrosusceptibility testing by the agar diskdiffusion test method (Kirby-Bauer).Samples are processed directly fromblood culture samples identified aspositive by a continuous monitoringblood culture system and confirmed asGram-negative rods by Gram stain.Organism identification must beconfirmed by an FDA cleared device fordirect testing from positive bloodculture before processing samples onthe eQUANT™ System.
Indication for Use
Device & PredicateDevices:	K223494Device	K231536Predicate
Source ofMicroorganisms	bacteria from positive blood cultures	Same
IndicatedAntimicrobial/OrganismCombinations	Amikacin: Acinetobacter baumanniicomplex, Escherichia coli, Klebsiellapneumoniae, PseudomonasaeruginosaAmoxicillin-Clavulanate:Escherichia coli, Klebsiella species(including K. oxytoca, K.pneumoniae), Proteus mirabilis,Proteus vulgarisAmpicillin: Escherichia coli, ProteusmirabilisAmpicillin-Sulbactam:Acinetobacter baumannii complex,Citrobacter koseri, Escherichia coli,Klebsiella pneumoniae, ProteusmirabilisCefazolin: Escherichia coli,Klebsiella pneumoniaeCefepime: Citrobacter freundiicomplex, Citrobacter koseri,Enterobacter cloacae complex,Escherichia coli, Klebsiellaaerogenes, Klebsiella oxytoca,Klebsiella pneumoniae, Morganellamorganii, Proteus mirabilis, Proteusvulgaris, Serratia marcescens,Pseudomonas aeruginosaCeftazidime: Escherichia coli,Klebsiella pneumoniae, PseudomonasaeruginosaCeftazidime-Avibactam: Citrobacterfreundii complex, Citrobacter koseri,Enterobacter cloacae complex,Escherichia coli, Klebsiellaaerogenes, Klebsiella oxytoca,Klebsiella pneumoniae, Morganellamorganii, Proteus mirabilis, Proteusvulgaris, Serratia marcescens,Pseudomonas aeruginosaCeftriaxone: Citrobacter freundiicomplex, Citrobacter koseri,Enterobacter cloacae complex,Escherichia coli, Klebsiellaaerogenes, Klebsiella oxytoca,Klebsiella pneumoniae, Proteusmirabilis	Amoxicillin/clavulanate: Escherichiacoli, Klebsiella oxytoca, Klebsiellapneumoniae, Proteus mirabilisAmpicillin: Escherichia coliAztreonam: Citrobacter freundii,Enterobacter cloacae, Escherichia coli,Klebsiella aerogenes, Klebsiellaoxytoca, Klebsiella pneumoniae,Proteus mirabilis, Proteus vulgaris,Serratia marcescens and PseudomonasaeruginosaCefazolin: Klebsiella pneumoniaeCefepime: Enterobacter cloacae,Escherichia coli, Klebsiella oxytoca,Klebsiella pneumoniae, Proteusmirabilis, Proteus vulgaris, Serratiamarcescens and PseudomonasaeruginosaCeftriaxone: Citrobacter freundii,Enterobacter cloacae, Escherichia coli,Klebsiella aerogenes, Klebsiellaoxytoca, Klebsiella pneumoniae,Proteus mirabilis, Proteus vulgaris,Serratia marcescensErtapenem: Citrobacter freundii,Enterobacter cloacae, Escherichia coli,Klebsiella aerogenes, Klebsiellaoxytoca, Klebsiella pneumoniae,Proteus mirabilis, Proteus vulgaris,Serratia marcescensGentamicin: Citrobacter freundii,Enterobacter cloacae, Escherichia coli,Klebsiella aerogenes, Klebsiellaoxytoca, Klebsiella pneumoniae,Proteus mirabilis, Proteus vulgaris,Serratia marcescens and PseudomonasaeruginosaLevofloxacin: Citrobacter freundii,Enterobacter cloacae, Escherichia coli,Klebsiella aerogenes, Klebsiellaoxytoca, Klebsiella pneumoniae,Proteus mirabilis, Proteus vulgaris,Serratia marcescens, and PseudomonasaeruginosaMeropenem: Acinetobacter spp.,Citrobacter freundii, Enterobacter
Device & PredicateDevices:	K223494Device	K231536Predicate
	Ciprofloxacin: Citrobacter freundiicomplex, Citrobacter koseri,Enterobacter cloacae complex,Escherichia coli, Klebsiellaaerogenes, Klebsiella oxytoca,Klebsiella pneumoniae, Morganellamorganii, Proteus mirabilis, Proteusvulgaris, Serratia marcescens,Pseudomonas aeruginosa	oxytoca, Klebsiella pneumoniae,Proteus mirabilis, Proteus vulgaris,Serratia marcescens, and Pseudomonasaeruginosa
	Piperacillin-Tazobactam:Acinetobacter baumannii complex,Citrobacter koseri, Escherichia coli,Klebsiella pneumoniae, Morganellamorganii, Proteus mirabilis, Proteusvulgaris, Serratia marcescens,Pseudomonas aeruginosa
	Ertapenem: Citrobacter freundiicomplex, Citrobacter koseri,Enterobacter cloacae complex,Escherichia coli, Klebsiellaaerogenes, Klebsiella oxytoca,Klebsiella pneumoniae, Morganellamorganii, Proteus mirabilis, Proteusvulgaris, Serratia marcescens
	Gentamicin: Citrobacter freundiicomplex, Citrobacter koseri,Enterobacter cloacae complex,Escherichia coli, Klebsiellaaerogenes, Klebsiella oxytoca,Klebsiella pneumoniae, Morganellamorganii, Proteus mirabilis, Proteusvulgaris, Serratia marcescens,Pseudomonas aeruginosa
	Imipenem: Acinetobacter baumanniicomplex, Escherichia coli, Klebsiellapneumoniae
	Meropenem: Acinetobacterbaumannii complex, Citrobacterfreundii complex, Citrobacter koseri,Enterobacter cloacae complex,Escherichia coli, Klebsiella oxytoca,Klebsiella pneumoniae, Morganellamorganii, Proteus mirabilis, Proteusvulgaris, Serratia marcescens,Pseudomonas aeruginosa
	Minocycline: Acinetobacterbaumannii complex, Escherichia coli,Klebsiella pneumoniae
	Piperacillin-Tazobactam:Acinetobacter baumannii complex,Citrobacter koseri, Escherichia coli,Klebsiella pneumoniae, Morganellamorganii, Proteus mirabilis, Proteusvulgaris, Serratia marcescens,Pseudomonas aeruginosa
		Piperacillin/tazobactam:Acinetobacter spp., Escherichia coli,Klebsiella pneumoniae, Proteusmirabilis, Proteus vulgaris, Serratiamarcescens, and Pseudomonasaeruginosa
		Tobramycin: Citrobacter freundii,Enterobacter cloacae, Escherichia coli,Klebsiella aerogenes, Klebsiellaoxytoca, Klebsiella pneumoniae,Proteus mirabilis, Proteus vulgaris,Serratia marcescens, and Pseudomonasaeruginosa
Device & PredicateDevices:	K223494Device	K231536Predicate
	Tobramycin: Escherichia coli,Klebsiella pneumoniae, Pseudomonasaeruginosa
Technology	Uses lysis, centrifugation andsequential optical densitymeasurements to generate aMcFarland-equivalent suspension.	Measure pathogen concentration viapotentiometric sensing of changes inoxidation-reduction potential (ORP)during pathogen metabolism. Usesspecies-specific and blood culture bottlespecific algorithms to determine when a0.5 McFarland equivalent concentrationis reached.
Output/ResultsReported	Liquid suspension of bacteria(McFarland equivalent) suitable forsusceptibility testing.	Same
AST	Selux AST System	Kirby-Bauer disc diffusion

{9}------------------------------------------------

{10}------------------------------------------------

{11}------------------------------------------------

Despite the differences between the PBC Separator with Selux AST System and the predicate device, the overall risk and safety of system use is not affected.

Reproducibility

PBC Separator with Selux AST System Intra- and inter-site reproducibility was evaluated by testing a minimum of 5 samples for each of 9 representative antimicrobials at each of three sites (2 external, 1 internal). Each sample comprised an isolate that was seeded at approximately 10-10,000 CFU into a blood culture bottle with approximately 10 mL of fresh human blood from a healthy donor and then loaded into an FDA-cleared continuous monitoring blood culture system (BD BACTEC, bioMerieux BacT/ALERT 3D, or bioMerieux BacT/ALERT VIRTUO) until positive growth was detected. The positive blood culture bottle was then removed and processed using the PBC Separator and Selux AST System. Each sample was tested in triplicate using three different inoculums prepared by the PBC Separator on each of three days it was tested at each site. There is thus a minimum of 3 × 3 = 9 results per sample and 9 × 5 = 45 results per antimicrobial at a single site. The intra-site reproducibility is given in the following table. In each case, the bestand worst-case intra-site reproducibility was ≥ 95%.

Intra-Site Reproducibility
Antimicrobial	N	Best-Case	Worst-Case
Ampicillin	45	100%	100%
Ampicillin-sulbactam	54	100%	100%
Amoxicillin-clavulanate	45	100%	100%
Cefazolin	45	100%	100%
Ceftazidime-avibactam	45	100%	100%
Ciprofloxacin	54	100%	100%

{12}------------------------------------------------

Intra-Site Reproducibility
Antimicrobial	N	Best-Case	Worst-Case
Gentamicin	54	100%	100%
Meropenem	63	98.4%	98.4%
Minocycline	54	98.1%	98.1%

For inter-site reproducibility, there are a minimum of 3 × 3 × 3 = 27 results per sample and 27 × 5 = 135 results per antimicrobial. The inter-site reproducibility is given in the following table. In each case, the best- and worst-case intra-site reproducibility was > 95%.

Inter-Site Reproducibility
Antimicrobial	N	Best-Case	Worst-Case
Ampicillin	135	99.30%	99.30%
Ampicillin-sulbactam	162	100%	100%
Amoxicillin-clavulanate	135	100%	100%
Cefazolin	135	100%	100%
Ceftazidime-avibactam	135	100%	100%
Ciprofloxacin	162	100%	100%
Gentamicin	162	98.5%	98.5%
Meropenem	189	95.8%	95.8%
Minocycline	162	96.3%	96.3%

Other Analytical Studies:

Post-Positivity Sample Stability Study

The amount of time between the registration of positive growth for a sample and the initiation of processing with the PBC Separator was evaluated. Selux AST System MIC results from samples processed with the PBC Separator 16 hours after registering positive growth in a continuous monitoring blood culture system were compared with t = 0 hr control MIC results from samples processed on the PBC Separator immediately after registering positive growth. At least two replicates of one species from each indicated antimicrobial/organism reporting group was tested per drug per timepoint. Every antimicrobial agent at the 16-hour timepoint had essential agreement (EA) > 95%compared with the 0-hour timepoint. The total EA for all results at the 16-hour timepoint compared with the 0-hour timepoint was 99.6% (264/265 results in EA). Positive blood bottles should be processed promptly after ringing positive on a continuous blood culture monitoring system. In the case of unavoidable delays or if the need for sample re-testing arises, bottles must be processed within 16 hours post ring.

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

Blood Culture Bottle Compatibility Study

Eleven types of blood culture bottles listed below were evaluated with the PBC Separator with Selux AST System.

Bottle Type	Blood Culture System Compatibility
BACTEC Plus Aerobic	BD BACTEC
BACTEC Plus Anaerobic	BD BACTEC
BACTEC Standard Aerobic	BD BACTEC
BACTEC Standard Anaerobic	BD BACTEC
BACTEC Lytic Anaerobic	BD BACTEC
BACTEC Peds Plus	BD BACTEC
BacT/ALERT FA Plus	BacT/ALERT 3D, VIRTUO
BacT/ALERT FN Plus	BacT/ALERT 3D, VIRTUO
BacT/ALERT SA	BacT/ALERT 3D, VIRTUO
BacT/ALERT SN	BacT/ALERT 3D, VIRTUO
BacT/ALERT PF Plus	BacT/ALERT 3D, VIRTUO

Bacterial samples were seeded at clinically relevant concentrations into the blood culture bottles with the manufacturer recommended volume of healthy donor human blood. Seeded bottles were loaded into either a BD BACTEC or bioMérieux BacT/ALERT continuous monitoring blood culture system and incubated until positivity. Positive blood culture samples were then processed with the PBC Separator with Selux AST System. At least two replicates of one species from each indicated drug/organism reporting group was tested per bottle type and evaluated with all claimed antimicrobials. Aerobic bottles were seeded with A. baumannii (complex), E. coli, K. pneumoniae, and P. aeruginosa, and anaerobic bottles were seeded with E. coli, K. pneumoniae, P. mirabilis, and M. morganii.

Selux AST System MIC results from all tested bottle types showed >89.9% essential agreement (EA) to the reference method. Across all aerobic bottle types there was 99.3% EA (1629/1640 results in EA) and each aerobic bottle type had EA ≥ 98.5%. Across all anaerobic bottle types there was 99.5% EA (974/979 results in EA) and each anaerobic bottle type had EA ≥ 98.5%.

PBC Separator with Selux AST System performance with bioMérieux aerobic bottles is provided in the table below.

Antimicrobial	IndicatedOrganism(s)	bioMérieuxBacT/ALERT SA		bioMérieuxBacT/ALERT FAPlus		bioMérieuxBacT/ALERTPF Plus
		# EA /Total	% EA	# EA /Total	% EA	# EA /Total	% EA
Amikacin	A. baumanniicomplex	9/9	100.0%	3/3	100.0%	3/3	100.0%
	Enterobacterales	28/28	100.0%	9/9	100.0%	8/8	100.0%
	P. aeruginosa	6/6	100.0%	3/3	100.0%	3/3	100.0%
	Combined	43/43	100.0%	15/15	100.0%	14/14	100.0%
Antimicrobial	IndicatedOrganism(s)		bioMérieuxBacT/ALERT SA		bioMérieuxBacT/ALERT FAPlus		bioMérieuxBacT/ALERTPF Plus
		# EA /Total	% EA	# EA /Total	% EA	# EA /Total	% EA
Amoxicillin-Clavulanate	Enterobacterales	28/28	100.0%	9/9	100.0%	8/8	100.0%
Ampicillin	Enterobacterales	22/22	100.0%	7/7	100.0%	6/6	100.0%
Ampicillin-Sulbactam	A. baumanniicomplex	9/9	100.0%	3/3	100.0%	3/3	100.0%
	Enterobacterales	28/28	100.0%	9/9	100.0%	8/8	100.0%
	Combined	37/37	100.0%	12/12	100.0%	11/11	100.0%
Cefazolin	Enterobacterales	28/28	100.0%	9/9	100.0%	8/8	100.0%
Cefepime	Enterobacterales	28/28	100.0%	9/9	100.0%	8/8	100.0%
	P. aeruginosa	6/6	100.0%	3/3	100.0%	3/3	100.0%
	Combined	34/34	100.0%	12/12	100.0%	11/11	100.0%
Ceftazidime	Enterobacterales	28/28	100.0%	9/9	100.0%	8/8	100.0%
	P. aeruginosa	3/3	100.0%	2/2	100.0%	3/3	100.0%
	Combined	31/31	100.0%	11/11	100.0%	11/11	100.0%
Ceftazidime-Avibactam	Enterobacterales	28/28	100.0%	9/9	100.0%	8/8	100.0%
	P. aeruginosa	6/6	100.0%	3/3	100.0%	3/3	100.0%
	Combined	34/34	100.0%	12/12	100.0%	11/11	100.0%
Ceftriaxone	Enterobacterales	28/28	100.0%	9/9	100.0%	8/8	100.0%
Ciprofloxacin	Enterobacterales	25/28	89.3%¹	9/9	100.0%	8/8	100.0%
	P. aeruginosa	6/6	100.0%	3/3	100.0%	3/3	100.0%
	Combined	31/34	91.2%	12/12	100.0%	11/11	100.0%
Ertapenem	Enterobacterales	28/28	100.0%	9/9	100.0%	8/8	100.0%
Gentamicin	Enterobacterales	28/28	100.0%	9/9	100.0%	8/8	100.0%
	P. aeruginosa	6/6	100.0%	3/3	100.0%	3/3	100.0%
	Combined	34/34	100.0%	12/12	100.0%	11/11	100.0%
Imipenem	A. baumanniicomplex	9/9	100.0%	3/3	100.0%	3/3	100.0%
	Enterobacterales	28/28	100.0%	9/9	100.0%	8/8	100.0%
	Combined	37/37	100.0%	12/12	100.0%	11/11	100.0%
Meropenem	A. baumanniicomplex	9/9	100.0%	3/3	100.0%	3/3	100.0%
	Enterobacterales	28/28	100.0%	9/9	100.0%	8/8	100.0%
	P. aeruginosa	6/6	100.0%	3/3	100.0%	3/3	100.0%
Antimicrobial	IndicatedOrganism(s)	bioMérieuxBacT/ALERT SA		bioMérieuxBacT/ALERT FA Plus		bioMérieuxBacT/ALERT PF Plus
		# EA /Total	% EA	# EA /Total	% EA	# EA /Total	% EA
	Combined	43/43	100.0%	15/15	100.0%	14/14	100.0%
Minocycline	A. baumanniicomplex	9/9	100.0%	2/3	66.7%	2/3	66.7%
	Enterobacterales	28/28	100.0%	9/9	100.0%	8/8	100.0%
	Combined	37/37	100.0%	11/12	91.7%	10/11	90.9%
Piperacillin-Tazobactam	A. baumanniicomplex	9/9	100.0%	3/3	100.0%	3/3	100.0%
	Enterobacterales	26/28	92.9%	9/9	100.0%	8/8	100.0%
	P. aeruginosa	6/6	100.0%	3/3	100.0%	3/3	100.0%
	Combined	41/43	95.3%	15/15	100.0%	14/14	100.0%
Tobramycin	Enterobacterales	28/28	100.0%	9/9	100.0%	8/8	100.0%
	P. aeruginosa	6/6	100.0%	3/3	100.0%	3/3	100.0%
	Combined	34/34	100.0%	12/12	100.0%	11/11	100.0%

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

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

1 Ciprofloxacin tested with Enterobacterales derived from bioMérieux BacT/ALERT SA bottles demonstrated an EA <90%. The data were deemed acceptable based on the totality of data.

PBC Separator with Selux AST System performance with BD BACTEC aerobic bottles is provided in the table below.

Antimicrobial	IndicatedOrganism(s)	BD BACTECStandardAerobic# EA / Total	BD BACTECStandardAerobic% EA	BD BACTECPlus Aerobic# EA / Total	BD BACTECPlus Aerobic% EA	BD BACTEC PedsPlus# EA / Total	BD BACTEC PedsPlus% EA
Amikacin	A. baumanniicomplex	8/8	100.0%	3/3	100.0%	1/2	50.0%1
	Enterobacterales	11/11	100.0%	10/10	100.0%	10/10	100.0%
	P. aeruginosa	6/6	100.0%	2/2	100.0%	3/3	100.0%
	Combined	25/25	100.0%	15/15	100.0%	14/15	93.3%
Amoxicillin-Clavulanate	Enterobacterales	11/11	100.0%	10/10	100.0%	10/10	100.0%
Ampicillin	Enterobacterales	5/5	100.0%	8/8	100.0%	8/8	100.0%
Ampicillin-Sulbactam	A. baumanniicomplex	8/8	100.0%	3/3	100.0%	2/2	100.0%
	Enterobacterales	11/11	100.0%	10/10	100.0%	10/10	100.0%
Antimicrobial	IndicatedOrganism(s)	BD BACTECStandardAerobic# EA / Total	BD BACTECStandardAerobic% EA	BD BACTECPlus Aerobic# EA / Total	BD BACTECPlus Aerobic% EA	BD BACTEC PedsPlus# EA / Total	BD BACTEC PedsPlus% EA
	Combined	19/19	100.0%	13/13	100.0%	12/12	100.0%
Cefazolin	Enterobacterales	11/11	100.0%	10/10	100.0%	10/10	100.0%
	Enterobacterales	11/11	100.0%	10/10	100.0%	10/10	100.0%
Cefepime	P. aeruginosa	6/6	100.0%	2/2	100.0%	3/3	100.0%
	Combined	17/17	100.0%	12/12	100.0%	13/13	100.0%
	Enterobacterales	11/11	100.0%	10/10	100.0%	10/10	100.0%
Ceftazidime	P. aeruginosa	5/5	100.0%	1/1	100.0%	2/2	100.0%
	Combined	16/16	100.0%	11/11	100.0%	12/12	100.0%
	Enterobacterales	11/11	100.0%	10/10	100.0%	10/10	100.0%
Ceftazidime-Avibactam	P. aeruginosa	6/6	100.0%	2/2	100.0%	3/3	100.0%
	Combined	17/17	100.0%	12/12	100.0%	13/13	100.0%
Ceftriaxone	Enterobacterales	11/11	100.0%	10/10	100.0%	10/10	100.0%
Ciprofloxacin	Enterobacterales	11/11	100.0%	10/10	100.0%	10/10	100.0%
	P. aeruginosa	6/6	100.0%	3/3	100.0%	3/3	100.0%
	Combined	17/17	100.0%	13/13	100.0%	13/13	100.0%
Ertapenem	Enterobacterales	11/11	100.0%	10/10	100.0%	10/10	100.0%
	Enterobacterales	11/11	100.0%	10/10	100.0%	10/10	100.0%
Gentamicin	P. aeruginosa	6/6	100.0%	3/3	100.0%	3/3	100.0%
	Combined	17/17	100.0%	13/13	100.0%	13/13	100.0%
	A. baumanniicomplex	8/8	100.0%	3/3	100.0%	2/2	100.0%
Imipenem	Enterobacterales	11/11	100.0%	10/10	100.0%	10/10	100.0%
	Combined	19/19	100.0%	13/13	100.0%	12/12	100.0%
	A. baumanniicomplex	8/8	100.0%	3/3	100.0%	2/2	100.0%
Meropenem	Enterobacterales	11/11	100.0%	10/10	100.0%	10/10	100.0%
	P. aeruginosa	6/6	100.0%	2/2	100.0%	3/3	100.0%
	Combined	25/25	100.0%	15/15	100.0%	15/15	100.0%
	A. baumanniicomplex	8/8	100.0%	3/3	66.7%	0/2	0.0%
Minocycline	Enterobacterales	11/11	100.0%	10/10	100.0%	10/10	100.0%
	Combined	19/19	100.0%	2/2	100.0%	10/12	83.3%
Antimicrobial	Indicated Organism(s)	BD BACTEC Standard Aerobic# EA / Total	BD BACTEC Standard Aerobic% EA	BD BACTEC Plus Aerobic# EA / Total	BD BACTEC Plus Aerobic% EA	BD BACTEC Peds Plus# EA / Total	BD BACTEC Peds Plus% EA
Piperacillin-Tazobactam	A. baumannii complex	8/8	100.0%	3/3	100.0%	2/2	100.0%
	Enterobacterales	11/11	100.0%	10/10	100.0%	10/10	100.0%
	P. aeruginosa	6/6	100.0%	2/2	100.0%	3/3	100.0%
	Combined	25/25	100.0%	15/15	100.0%	15/15	100.0%
Tobramycin	Enterobacterales	11/11	100.0%	10/10	100.0%	10/10	100.0%
	P. aeruginosa	6/6	100.0%	2/2	100.0%	3/3	100.0%
	Combined	17/17	100.0%	12/12	100.0%	13/13	100.0%

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

{17}------------------------------------------------

1 Amikacin tested with 4. baumannii derived from BD BACTEC Peds Plus bottles demonstrated an EA <90%. The
data were deemed acceptable based on the totality of data.

PBC Separator with Selux AST System performance with anaerobic blood bottles is provided in
the table below.

Drug	OrganismGroup	BD BACTEC StandardAnaerobic		BD BACTEC PlusAnaerobic		BD BACTECLytic Anaerobic		bioMerieuxBacT/ALERT SN		bioMerieuxBacT/ALERT FNPlus
		#EA / Tot	%EA	#EA /Tot	%EA	#EA /Tot	%EA	#EA /Tot	%EA	#EA /Tot	%EA
Amikacin	Enterobacterales	13/13	100.00%	9/9	100.00%	10/10	100.00%	6/6	100.00%	9/9	100.00%
Amoxicillin-clavulanate	Enterobacterales	15/15	100.00%	11/11	100.00%	12/12	100.00%	8/8	100.00%	11/11	100.00%
Ampcillin	Enterobacterales	13/13	100.00%	9/9	100.00%	10/10	100.00%	6/6	100.00%	9/9	100.00%
Ampicillin-sulbactam	Enterobacterales	17/17	100.00%	13/13	100.00%	13/14	92.90%	10/10	100.00%	13/13	100.00%
Cefazolin	Enterobacterales	13/13	100.00%	9/9	100.00%	10/10	100.00%	6/6	100.00%	9/9	100.00%
Cefepime	Enterobacterales	17/17	100.00%	13/13	100.00%	14/14	100.00%	10/10	100.00%	13/13	100.00%
Ceftazidime	Enterobacterales	13/13	100.00%	9/9	100.00%	10/10	100.00%	6/6	100.00%	9/9	100.00%
Ceftazidime-avibactam	Enterobacterales	17/17	100.00%	13/13	100.00%	14/14	100.00%	10/10	100.00%	13/13	100.00%
Ceftriaxone	Enterobacterales	15/15	100.00%	11/11	100.00%	12/12	100.00%	8/8	100.00%	11/11	100.00%
Ciprofloxacin	Enterobacterales	17/17	100.00%	13/13	100.00%	12/14	85.7%	10/10	100.00%	12/13	92.30%
Ertapenem	Enterobacterales	17/17	100.00%	13/31	100.00%	14/14	100.00%	10/10	100.00%	13/31	100.00%
Gentamicin	Enterobacterales	17/17	100.00%	13/13	100.00%	14/14	100.00%	10/10	100.00%	13/13	100.00%
Imipenem	Enterobacterales	13/13	100.00%	9/9	100.00%	10/10	100.00%	6/6	100.00%	9/9	100.00%
Meropenem	Enterobacterales	17/17	100.00%	13/13	100.00%	14/14	100.00%	10/10	100.00%	13/13	100.00%

{18}------------------------------------------------

Drug	OrganismGroup	BD BACTEC StandardAnaerobic		BD BACTEC PlusAnaerobic		BD BACTECLytic Anaerobic		bioMerieuxBacT/ALERT SN		bioMerieuxBacT/ALERT FNPlus
		#EA / Tot	%EA	#EA /Tot	%EA	#EA /Tot	%EA	#EATot	%EA	#EA .Tot	%EA
Minocycline	Enterobacterales	13/13	100.00%	9/9	100.00%	10/10	100.00%	6/6	100.00%	9/9	100.00%
Piperacillin-tazobactam	Enterobacterales	17/17	100.00%	13/13	100.00%	14/14	100.00%	10/10	100.00%	13/13	100.00%
Tobramycin	Enterobacterales	13/13	100.00%	9/9	100.00%	10/10	100.00%	6/6	100.00%	9/9	100.00%

Interfering Substances Testing

The effect of the presence of endogenous and exogenous interferents that may be present in a blood culture was evaluated on the PBC Separator with Selux AST System. Studies were performed by seeding at least one species for each reporting group for each antimicrobial at clinically relevant concentrations into non-resin blood culture bottles with the manufacturer recommended volume of human blood. Potential interferents were seeded into the blood culture bottles at the time of bacterial seeding and prior to incubation in the blood culture system. Control samples to which no interferents were added were processed in parallel. Seeded bottles were loaded into a continuous monitoring blood culture system and incubated until positive blood culture samples were then processed with the PBC Separator with Selux AST System.

Endogenous interferents evaluated on the system included red blood cells (RBCs), white blood cells (WBCs), platelets, triglycerides, gamma globulin, and conjugated and unconjugated bilirubin. Exogenous interferents included available oral antibiotics, including cefpodoxime, ciprofloxacin, penicillin, and gentamicin. Each was spiked into a non-resin blood culture bottle with healthy donor blood at the peak serum level for oral administration of each agent. Seeded microbial organisms were selected that had resistance to the exogenous antibiotic under test.

The PBC Separator with Selux AST System MIC results showed >89.9% EA for every interferent tested when compared with PBC Separator with Selux AST System results for the same organism run in a control condition (no interferent).

		Red Blood Cells(20 g/dL)		White Blood Cells(12,000 cells/µL)		Platelets(450,000/μL)		Gamma Globulins(50 g/L)
Antimicrobial	Indicated Organism(s)	# EA /Total	% EA	# EA /Total	% EA	# EA /Total	% EA	# EA /Total	% EA
Amikacin	A. baumannii complex	2/2	100.0%	4/4	100.0%	3/3	100.0%	3/3	100.0%
	Enterobacterales	11/11	100.0%	5/5	100.0%	5/5	100.0%	10/10	100.0%
	P. aeruginosa	2/2	100.0%	5/5	100.0%	4/4	100.0%	4/4	100.0%
	Combined	15/15	100.0%	14/14	100.0%	12/12	100.0%	17/17	100.0%
		Red Blood Cells(20 g/dL)		White Blood Cells(12,000 cells/μL)		Platelets(450,000/μL)		Gamma Globulins(50 g/L)
Antimicrobial	Indicated Organism(s)	# EA / Total	% EA	# EA / Total	% EA	# EA / Total	% EA	# EA / Total	% EA
Amoxicillin-Clavulanate	Enterobacterales	11/11	100.0%	5/5	100.0%	5/5	100.0%	10/10	100.0%
Ampicillin	Enterobacterales	9/9	100.0%	4/4	100.0%	4/4	100.0%	8/8	100.0%
	A. baumannii complex	/2/	100.0%	4/4	100.0%	5/5	100.0%	4/4	100.0%
Ampicillin-Sulbactam	Enterobacterales	11/11	100.0%	5/5	100.0%	5/5	100.0%	10/10	100.0%
	Combined	13/13	100.0%	9/9	100.0%	10/10	100.0%	14/14	100.0%
Cefazolin	Enterobacterales	11/11	100.0%	5/5	100.0%	5/5	100.0%	10/10	100.0%
	Enterobacterales	11/11	100.0%	5/5	100.0%	5/5	100.0%	10/10	100.0%
Cefepime	P. aeruginosa	2/2	100.0%	5/5	100.0%	4/4	100.0%	4/4	100.0%
	Combined	13/13	100.0%	10/10	100.0%	9/9	100.0%	14/14	100.0%
	Enterobacterales	11/11	100.0%	5/5	100.0%	5/5	100.0%	10/10	100.0%
Ceftazidime	P. aeruginosa	1/1	100.0%	4/4	100.0%	4/4	100.0%	2/2	100.0%
	Combined	12/12	100.0%	9/9	100.0%	9/9	100.0%	12/12	100.0%
	Enterobacterales	11/11	100.0%	5/5	100.0%	5/5	100.0%	10/10	100.0%
Ceftazidime-Avibactam	P. aeruginosa	2/2	100.0%	5/5	100.0%	4/4	100.0%	4/4	100.0%
	Combined	13/13	100.0%	10/10	100.0%	9/9	100.0%	14/14	100.0%
Ceftriaxone	Enterobacterales	11/11	100.0%	5/5	100.0%	5/5	100.0%	10/10	100.0%
	Enterobacterales	11/11	100.0%	5/5	100.0%	5/5	100.0%	10/10	100.0%
Ciprofloxacin	P. aeruginosa	2/2	100.0%	5/5	100.0%	4/4	100.0%	4/4	100.0%
	Combined	13/13	100.0%	10/10	100.0%	9/9	100.0%	14/14	100.0%
Ertapenem	Enterobacterales	11/11	100.0%	5/5	100.0%	5/5	100.0%	10/10	100.0%
	Enterobacterales	11/11	100.0%	5/5	100.0%	5/5	100.0%	10/10	100.0%
Gentamicin	P. aeruginosa	2/2	100.0%	5/5	100.0%	4/4	100.0%	4/4	100.0%
	Combined	13/13	100.0%	10/10	100.0%	9/9	100.0%	14/14	100.0%
	A. baumannii complex	2/2	100.0%	4/4	100.0%	5/5	100.0%	4/4	100.0%
Imipenem	Enterobacterales	11/11	100.0%	5/5	100.0%	5/5	100.0%	10/10	100.0%
	Combined	13/13	100.0%	9/9	100.0%	10/10	100.0%	14/14	100.0%
	A. baumannii complex	2/2	100.0%	4/4	100.0%	5/5	100.0%	4/4	100.0%
Meropenem	Enterobacterales	11/11	100.0%	5/5	100.0%	5/5	100.0%	10/10	100.0%
	P. aeruginosa	2/2	100.0%	5/5	100.0%	4/4	100.0%	4/4	100.0%
		Red Blood Cells(20 g/dL)			White Blood Cells(12,000 cells/μL)		Platelets(450,000/μL)	Gamma Globulins(50 g/L)
Antimicrobial	Indicated Organism(s)	# EA /Total	% EA	# EA /Total	% EA	# EA /Total	% EA	# EA /Total	% EA
	Combined	15/15	100.0%	14/14	100.0%	14/14	100.0%	18/18	100.0%
	A. baumannii complex	2/2	100.0%	4/4	100.0%	5/5	100.0%	4/4	100.0%
Minocycline	Enterobacterales	11/11	100.0%	5/5	100.0%	5/5	100.0%	10/10	100.0%
	Combined	13/13	100.0%	9/9	100.0%	10/10	100.0%	14/14	100.0%
	A. baumannii complex	2/2	100.0%	4/4	100.0%	3/6	60.0%	4/4	100.0%
Piperacillin-Tazobactam 1	Enterobacterales	2/11	18.2%	1/5	20.0%	1/5	20.0%	2/10	20.0%
	P. aeruginosa	2/2	100.0%	5/5	100.0%	4/4	100.0%	4/4	100.0%
	Combined	6/15	40.0%	10/14	71.4%	8/14	57.1%	10/18	55.6%
Tobramycin	Enterobacterales	10/11	90.9%	4/5	80.0%	5/5	100.0%	9/10	90.0%
	P. aeruginosa	2/2	100.0%	5/5	100.0%	4/4	100.0%	4/4	100.0%
	Combined	12/13	92.3%	9/10	90.0%	9/9	100.0%	13/14	92.9%

{19}------------------------------------------------

{20}------------------------------------------------

1 An essential agreement <90% and very major errors were observed when testing Piperacillin-Tazobactam with K. pneumoniae with all evaluated potential endogenous interferents.

Antimicrobial	Indicated Organism(s)		ConjugatedBilirubin(475 µmol/L)		UnconjugatedBilirubin(684 µmol/L)	Triglycerides(16.94 mmol/L)
		# EA /Total	% EA	# EA /Total	% EA	# EA /Total	% EA
Amikacin	A. baumannii complex	2/2	100.0%	2/2	100.0%	1/1	100.0%
Amikacin	Enterobacterales	11/11	100.0%	11/11	100.0%	7/7	100.0%
Amikacin	P. aeruginosa	2/2	100.0%	2/2	100.0%	2/3	66.7%
Amikacin	Combined	15/15	100.0%	15/15	100.0%	10/11	100.0%
Amoxicillin-Clavulanate	Enterobacterales	11/11	100.0%	11/11	100.0%	7/7	100.0%
Ampicillin	Enterobacterales	9/9	100.0%	9/9	100.0%	5/5	100.0%
Ampicillin-Sulbactam	A. baumannii complex	2/2	100.0%	2/2	100.0%	3/3	100.0%
Ampicillin-Sulbactam	Enterobacterales	11/11	100.0%	11/11	100.0%	7/7	100.0%
Ampicillin-Sulbactam	Combined	13/13	100.0%	13/13	100.0%	10/10	100.0%
Cefazolin	Enterobacterales	11/11	100.0%	11/11	100.0%	7/7	100.0%
Cefepime	Enterobacterales	11/11	100.0%	11/11	100.0%	7/7	100.0%
Cefepime	P. aeruginosa	2/2	100.0%	2/2	100.0%	3/3	100.0%
		ConjugatedBilirubin(475 µmol/L)		UnconjugatedBilirubin(684 µmol/L)		Triglycerides(16.94 mmol/L)
Antimicrobial	Indicated Organism(s)	# EA /Total	% EA	# EA /Total	% EA	# EA /Total	% EA
	Combined	13/13	100.0%	13/13	100.0%	10/10	100.0%
	Enterobacterales	11/11	100.0%	11/11	100.0%	7/7	100.0%
Ceftazidime	P. aeruginosa	2/2	100.0%	1/1	100.0%	3/3	100.0%
	Combined	13/13	100.0%	12/12	100.0%	10/10	100.0%
	Enterobacterales	11/11	100.0%	11/11	100.0%	7/7	100.0%
Ceftazidime-Avibactam	P. aeruginosa	2/2	100.0%	2/2	100.0%	3/3	100.0%
	Combined	13/13	100.0%	13/13	100.0%	10/10	100.0%
Ceftriaxone	Enterobacterales	11/11	100.0%	11/11	100.0%	7/7	100.0%
	Enterobacterales	11/11	100.0%	11/11	100.0%	7/7	100.0%
Ciprofloxacin	P. aeruginosa	2/2	100.0%	2/2	100.0%	3/3	100.0%
	Combined	13/13	100.0%	13/13	100.0%	10/10	100.0%
Ertapenem	Enterobacterales	11/11	100.0%	11/11	100.0%	7/7	100.0%
	Enterobacterales	11/11	100.0%	11/11	100.0%	7/7	100.0%
Gentamicin	P. aeruginosa	2/2	100.0%	2/2	100.0%	3/3	100.0%
	Combined	13/13	100.0%	13/13	100.0%	10/10	100.0%
	A. baumannii complex	2/2	100.0%	2/2	100.0%	3/3	100.0%
Imipenem	Enterobacterales	11/11	100.0%	11/11	100.0%	7/7	100.0%
	Combined	13/13	100.0%	13/13	100.0%	10/10	100.0%
	A. baumannii complex	2/2	100.0%	2/2	100.0%	3/3	100.0%
Meropenem	Enterobacterales	11/11	100.0%	11/11	100.0%	7/7	100.0%
	P. aeruginosa	2/2	100.0%	2/2	100.0%	3/3	100.0%
	Combined	15/15	100.0%	15/15	100.0%	13/13	100.0%
	A. baumannii complex	2/2	100.0%	2/2	100.0%	3/3	100.0%
Minocycline	Enterobacterales	11/11	100.0%	11/11	100.0%	7/7	100.0%
	Combined	13/13	100.0%	13/13	100.0%	10/10	100.0%
	A. baumannii complex	2/2	100.0%	2/2	100.0%	2/3	66.7%
Piperacillin-Tazobactam 1	Enterobacterales	3/11	27.3%	2/11	18.2%	2/7	28.6%
	P. aeruginosa	2/2	100.0%	2/2	100.0%	3/3	100.0%
	Combined	7/15	46.7%	6/15	40.0%	7/13	58.3%
Antimicrobial	Indicated Organism(s)	ConjugatedBilirubin(475 umol/L)		Bilirubin	Unconjugated(684 umol/L)	Triglycerides(16.94 mmol/L)
		# EA /Total	% EA	# EA /Total	% EA	# EA /Total	% EA
	Enterobacterales	10/11	90.9%	10/11	90.9%	6/7	85.7%
Tobramycin	P. aeruginosa	2/2	100.0%	2/2	100.0%	3/3	100.0%
	Combined	12/13	92.3%	12/13	92.3%	9/10	90.0%

{21}------------------------------------------------

{22}------------------------------------------------

1 An essential agreement <90% and very major errors were observed when testing Piperacillin-Tazobactam with K. pneumoniae with all evaluated potential endogenous interferents.

			Cefpodoxime(2.3 µg/mL)	Ciprofloxacin(3.6 µg/mL)		Gentamicin(24 µg/mL)		Penicillin(6.0 µg/mL)
Antimicrobial	Indicated Organism(s)	# EA /Total	% EA	# EA /Total	% EA	# EA /Total	% EA	# EA /Total	% EA
	A. baumannii complex	2/2	100.0%	2/2	100.0%	2/2	100.0%	2/2	100.0%
Amikacin	Enterobacterales	9/9	100.0%	10/10	100.0%	10/10	100.0%	10/11	90.9%
	P. aeruginosa	2/2	100.0%	2/2	100.0%	2/2	100.0%	2/2	100.0%
	Combined	13/13	100.0%	14/14	100.0%	14/14	100.0%	14/15	93.3%
Amoxicillin-Clavulanate	Enterobacterales	9/9	100.0%	10/10	100.0%	10/10	100.0%	10/11	90.9%
Ampicillin	Enterobacterales	7/7	100.0%	8/8	100.0%	8/8	100.0%	9/9	100.0%
Ampicillin-Sulbactam	A. baumannii complex	2/2	100.0%	2/2	100.0%	2/2	100.0%	2/2	100.0%
	Enterobacterales	9/9	100.0%	10/10	100.0%	10/10	100.0%	11/11	100.0%
	Combined	11/11	100.0%	12/12	100.0%	12/12	100.0%	13/13	100.0%
Cefazolin	Enterobacterales	9/9	100.0%	10/10	100.0%	10/10	100.0%	11/11	100.0%
	Enterobacterales	7/9	77.8%	9/10	90.0%	8/10	80.0%	11/11	100.0%
Cefepime	P. aeruginosa	2/2	100.0%	2/2	100.0%	2/2	100.0%	2/2	100.0%
	Combined	9/11	81.8%	11/12	91.7%	10/12	83.3%	13/13	100.0%
	Enterobacterales	9/9	100.0%	10/10	100.0%	10/10	100.0%	11/11	100.0%
Ceftazidime	P. aeruginosa	0/0	N/A 1	0/0	N/A 1	1/1	100.0%	1/1	100.0%
	Combined	9/9	100.0%	10/10	100.0%	11/11	100.0%	12/12	100.0%
	Enterobacterales	9/9	100.0%	10/10	100.0%	10/10	100.0%	10/11	90.9%
Ceftazidime-Avibactam	P. aeruginosa	2/2	100.0%	2/2	100.0%	2/2	100.0%	2/2	100.0%
	Combined	11/11	100.0%	12/12	100.0%	12/12	100.0%	12/13	92.3%
Ceftriaxone	Enterobacterales	9/9	100.0%	10/10	100.0%	10/10	100.0%	11/11	100.0%
			Cefpodoxime(2.3 µg/mL)	Ciprofloxacin(3.6 µg/mL)		Gentamicin(24 µg/mL)		Penicillin(6.0 µg/mL)
Antimicrobial	Indicated Organism(s)	# EA /Total	% EA	# EA /Total	% EA	# EA /Total	% EA	# EA /Total	% EA
Ciprofloxacin	Enterobacterales	9/9	100.0%	10/10	100.0%	10/10	100.0%	11/11	100.0%
	P. aeruginosa	2/2	100.0%	2/2	100.0%	2/2	100.0%	2/2	100.0%
	Combined	11/11	100.0%	12/12	100.0%	12/12	100.0%	13/13	100.0%
Ertapenem	Enterobacterales	9/9	100.0%	10/10	100.0%	10/10	100.0%	11/11	100.0%
Gentamicin	Enterobacterales	9/9	100.0%	10/10	100.0%	10/10	100.0%	11/11	100.0%
	P. aeruginosa	2/2	100.0%	2/2	100.0%	2/2	100.0%	2/2	100.0%
	Combined	11/11	100.0%	12/12	100.0%	12/12	100.0%	13/13	100.0%
Imipenem	A. baumannii complex	2/2	100.0%	2/2	100.0%	2/2	100.0%	2/2	100.0%
	Enterobacterales	5/9	55.6%	9/10	90.0%	7/10	70.0%	11/11	100.0%
	Combined	7/11	63.6%	11/12	91.7%	9/12	75.0%	13/13	100.0%
Meropenem	A. baumannii complex	2/2	100.0%	2/2	100.0%	2/2	100.0%	2/2	100.0%
	Enterobacterales	9/9	100.0%	10/10	100.0%	10/10	100.0%	11/11	100.0%
	P. aeruginosa	2/2	100.0%	2/2	100.0%	2/2	100.0%	2/2	100.0%
	Combined	13/13	100.0%	14/14	100.0%	14/14	100.0%	15/15	100.0%
Minocycline	A. baumannii complex	2/2	100.0%	2/2	100.0%	2/2	100.0%	2/2	100.0%
	Enterobacterales	8/9	88.9%	10/10	100.0%	10/10	100.0%	11/11	100.0%
	Combined	11/11	100.0%	12/12	100.0%	12/12	100.0%	13/13	100.0%
Piperacillin-Tazobactam	A. baumannii complex	2/2	100.0%	2/2	100.0%	2/2	100.0%	2/2	100.0%
	Enterobacterales	9/9	100.0%	10/10	90.0%	10/10	100.0%	11/11	100.0%
	P. aeruginosa	2/2	100.0%	2/2	100.0%	2/2	100.0%	2/2	100.0%
	Combined	13/13	100.0%	14/14	91.7%	14/14	100.0%	15/15	100.0%
Tobramycin	Enterobacterales 1	7/9	77.8%	10/10	100.0%	10/10	100.0%	11/11	100.0%
	P. aeruginosa	2/2	100.0%	2/2	97.0%	2/2	100.0%	2/2	100.0%
	Combined	9/11	81.8%	12/12	100.0%	12/12	100.0%	13/13	100.0%

{23}------------------------------------------------

1 An essential agreement <90% and minor errors were observed when testing Tobramycin with E. coli and K. pneumoniae with the potential interferent cefpodoxime.

Carry-Over/Cross-Contamination Study

Evaluation of carry-over/cross-contamination on the PBC Separator was performed by alternately processing samples of E. coli and K. pneumoniae with different AST profiles. Seeded bottles were loaded into a continuous monitoring blood culture system and incubated until positivity. Five E. coli and five K. pneumoniae positive blood culture samples were loaded onto a PBC Separator

{24}------------------------------------------------

across five runs. Each run comprised simultaneous processing of one E. coli and one K. pneumoniae sample. Samples were run on the Selux AST System. There were thus a total of five AST panels processed for each organism. Selux AST System MIC results showed >89.9% EA to the broth microdilution reference method result. The EA for E. coli was 100% (60/60 results in EA) and the EA for K. pneumoniae was 98.2% (54/55 results in EA). Additionally, there was no contamination observed on purity plates.

Clinical Studies

The following table gives the antimicrobial-organism combinations tested and includes the reporting range and breakpoints of each combination.

Antimicrobial	Abbreviation	TargetedOrganism	SeluxSystemReportingRange	AST Breakpoints
Amikacin	AMK	A. baumannii(complex)EnterobacteralesP. aeruginosa	≤0.12 to ≥256≤2 to ≥256≤0.12 to ≥256	≤16 / 32 / ≥64≤16 / 32 / ≥64≤16 / 32 / ≥64
Amoxicillin-Clavulanate	AMC	Enterobacterales	≤2 to ≥128	≤8 / 16 / ≥32
Ampicillin	AMP	Enterobacterales	≤2 to ≥128	≤8 / 16 / ≥32
Ampicillin-Sulbactam	SAM	A. baumannii(complex)Enterobacterales	≤2 to ≥128≤0.5 to ≥128	≤8 / 16 / ≥32≤8 / 16 / ≥32
Cefazolin	CFZ	Enterobacterales	≤0.12 to ≥128	≤2 / 4 / ≥8
Cefepime	FEP	EnterobacteralesP. aeruginosa	≤0.5 to ≥32≤0.25 to ≥128	≤2 / 4-8 / ≥16≤8 / ≥16
Ceftazidime	CAZ	EnterobacteralesP. aeruginosa	≤0.25 to ≥64≤0.25 to ≥256	≤4 / 8 / ≥16≤8 / ≥16
Ceftazidime-Avibactam	CZA	EnterobacteralesP. aeruginosa	≤0.12 to ≥64≤0.12 to ≥64	≤8 / ≥16≤8 / ≥16
Ceftriaxone	CRO	Enterobacterales	≤0.25 to ≥32	≤1 / 2 / ≥4
Ciprofloxacin	CIP	EnterobacteralesP. aeruginosa	≤0.03 to ≥16≤0.03 to ≥16	≤0.25 / 0.5 / ≥1≤0.5 / 1 / ≥2
Ertapenem	ETP	Enterobacterales	≤0.03 to ≥16	≤0.5 / 1 / ≥2
Gentamicin	GEN	EnterobacteralesP. aeruginosa	≤1 to ≥64≤0.5 to ≥64	≤4 / 8 / ≥16≤4 / 8 / ≥16
Imipenem	IMP	A. baumannii(complex)Enterobacterales	≤0.5 to ≥64≤0.25 to ≥16	≤2 / 4 / ≥8≤1 / 2 / ≥4
Meropenem	MEM	A. baumannii(complex)EnterobacteralesP. aeruginosa	≤0.12 to ≥64≤0.12 to ≥64≤0.12 to ≥64	≤2 / 4 / ≥8≤1 / 2 / ≥4≤2 / 4 / ≥8

{25}------------------------------------------------

Antimicrobial	Abbreviation	TargetedOrganism	SeluxSystemReportingRange	AST Breakpoints
Minocycline	MIN	A. baumannii(complex)Enterobacterales	≤0.25 to ≥64	≤4 / 8 / ≥16
Piperacillin-Tazobactam	TZP	A. baumannii(complex)EnterobacteralesP. aeruginosa	≤4 to ≥512	≤16 / 32-64 / ≥128
Tobramycin	TOB	EnterobacteralesP. aeruginosa	≤0.12 to ≥128	≤4 / 8 / ≥16

Clinical performance testing with the PBC Separator with Selux AST System was performed at four test sites using fresh positive blood culture samples left over from routine clinical care and seeded samples. Seeded samples were prepared using banked frozen isolates seeded at 10-10,000 CFU into blood culture bottles together with approximately 10 mL of fresh human blood from a healthy donor and then loaded into an FDA-cleared continuous monitoring blood culture system until positive growth was detected. Positive blood bottles were tested with the PBC Separator and Selux AST System. Fresh positive blood culture samples were collected from two clinical sites serving all boroughs of New York City and seeded samples were chosen to represent geographic diversity across the continental U.S. A total of 469 clinical (162 fresh and 307 seeded) and 87 challenge isolates from 12 Enterobacterales species, Acinetobacter baumannii complex, and Pseudomonas aeruginosa were tested to evaluate the PBC Separator performance for 17 antimicrobials with the Selux AST System. Depending on the spectrum of activity, breakpoints, and the claimed organisms (species/group) for each antimicrobial on the panel, the number of datapoints for the various antimicrobial-organisms tested varied and ranged from 38 (e.g. A. baumannii/Amikacin) to 469 (e.g. Enterobacterales/Ciprofloxacin).

PBC Separator with Selux AST System performance was determined by comparing Selux AST System results from PBC Separator-prepared inoculums to triplicate broth microdilution results performed at an independent reference laboratory. The PBC Separator with the Selux AST System meets performance criteria for each indication and is given in the following table, where performance is summarized by drug and reporting group. Additionally, QC testing was performed every day testing was performed at each site and met the 95% performance criteria for all antimicrobials.

{26}------------------------------------------------

Antimicrobial	Organism Group	TotalTested	# in EA	% EA	Total Eval	# Eval inEA	% EA ofEval	# in CA	% CA	# R	# VMJ	# MAJ	# MIN
Amikican	A. baumannii (complex)	38	35	92.1	23	20	87	36	94.7	17	0	0	2
	Enterobacterales	216	208	96.3	24	16	66.7	213	98.6	8	0	0	3
	P. aeruginosa	44	42	95.5	43	41	95.3	40	90.9	6	0	0	4
Amoxicillin-Clavulanate	Enterobacterales	330	328	99.4	222	220	99.1	295	89.4	39	0	0	35
Ampicillin	Enterobacterales	149	148	99.3	4	3	75	148	99.3	96	0	0	1
Ampicillin-Sulbactam	A. baumannii (complex)	40	37	92.5	21	18	85.7	38	95	25	0	0	2
	Enterobacterales	352	347	98.6	303	298	98.3	306	86.9	135	0	0	46
Cefazolin	Enterobacterales	207	197	95.2	118	108	91.5	187	90.3	99	1	0	19
Cefepime	Enterobacterales	406	396	97.5	35	25	71.4	390	96.1	61	0	0	16
	P. aeruginosa	43	42	97.7	37	36	97.3	42	97.7	11	0	0	0
Ceftazidime	Enterobacterales	217	215	99.1	66	64	97	204	94	70	0	0	13
	P. aeruginosa	40	40	100	35	35	100	40	100	9	0	0	0
Ceftazidime-Avibactam	Enterobacterales	418	409	97.8	96	87	90.6	418	100	4	0	0	0
	P. aeruginosa	43	43	100	39	39	100	42	97.7	9	0	0	0
Ceftriaxone	Enterobacterales	373	370	99.2	18	15	83.3	370	99.2	111	0	1	2
Ciprofloxacin	Enterobacterales	469	461	98.3	82	74	90.2	457	97.4	117	0	1	11
	P. aeruginosa	43	43	100	32	32	100	42	97.7	13	0	0	1
Ertapenem	Enterobacterales	412	405	98.3	62	55	88.7	408	99	28	0	0	4
Gentamicin	Enterobacterales	466	459	98.5	33	26	78.8	459	98.5	64	0	1	6
	P. aeruginosa	43	42	97.7	31	30	96.8	42	97.7	8	0	0	1
Imipenem	A. baumannii (complex)	39	38	97.4	4	3	75	39	100	26	0	0	0
	Enterobacterales	213	205	96.2	14	6	42.9	209	98.1	20	0	1	3
Meropenem	A. baumannii (complex)	39	37	94.9	14	12	85.7	39	100	27	0	0	0
	Enterobacterales	394	388	98.5	19	13	68.4	390	99	19	0	0	4
	P. aeruginosa	43	40	93	28	25	89.3	39	90.7	13	0	0	4
Minocycline	A. baumannii (complex)	39	38	97.4	24	23	95.8	33	84.6	12	0	0	6
	Enterobacterales	218	209	95.9	193	184	95.3	195	89.4	32	0	2	21
Piperacillin-Tazobactam	A. baumannii (complex)	39	37	94.9	5	3	60	38	97.4	27	0	0	1
	Enterobacterales	320	313	97.8	36	29	80.6	312	97.5	37	0	1	7
	P. aeruginosa	43	42	97.7	40	39	97.5	42	97.7	9	0	0	1
Tobramycin	Enterobacterales	216	207	95.8	200	191	95.5	200	92.6	49	0	0	16
	P. aeruginosa	43	41	95.3	37	35	94.6	41	95.3	10	0	0	2

*Selux MIC values for the following antimicrobial/organism combinations tended to be one doubling dilution lower than the reference MIC value:

Amikacin: A. baumannii (complex), E. coli, K. pneumoniae
. Amoxicillin-clavulanate: K. pneumoniae
Ampicillin: E. coli ●
Cefazolin: E. coli, K. pneumoniae .
Cefepime: P. aeruginosa, C. freundii complex, K. oxytoca ●
Ceftazidime: P. aeruginosa ●
Ciprofloxacin: E. coli .
. Gentamicin: E. coli, K. pneumoniae
Piperacillin-tazobactam: A. baumannii (complex), E. coli, S. marcescens, C. koseri

**Selux MIC values for the following antimicrobial/organism combinations tended to be one doubling dilution higher than the reference MIC value:

Cefepime: E. cloacae (complex), E. coli, K. pneumoniae
Ceftazidime: E. coli, K. pneumoniae ●
Ceftazidime-avibactam: C. freundii (complex), C. koseri, E. coli, K. aerogenes, K. oxytoca, K. pneumoniae, M. ● morganii, P. mirabilis, P. vulgaris
Ceftriaxone: C. freundii (complex), C. koseri, K. aerogenes, K. oxytoca, P. mirabilis, S. marcescens
. Ciprofloxacin: C. freundii (complex), C. koseri, E. cloacae (complex), K. aerogenes, K. oxytoca, M. morganii, P. mirabilis, P. vulgaris, S. marcescens
. Ertapenem: C. freundii (complex), C. koseri, E. cloacae (complex), K. oxytoca, P. mirabilis, P. vulgaris, S. marcescens
. Gentamicin: P. mirabilis
. Imipenem: K. pneumoniae
Meropenem: C. freundii (complex), C. koseri, E. cloacae (complex), K. pneumonia, M. morganii, P. mirabilis, P. vulgaris, S. marcescens
. Minocycline: A. baumannii (complex)

***Perform an alternative method of testing prior to reporting of results for the following antibiotic/organism combination: Ampicillin-Sulbactam: K. oxytoca, M. morganii

***Perform an alternative method of testing prior to results for the following antibiotic/organism combination: Cefazolin-E. coli when the Selux AST System MIC is 4 ug/mL due to the occurrence of minor errors, that were in essential agreement, resulting in a category agreement below 90%.

{27}------------------------------------------------

Conclusion

Based on our studies and testing, the PBC Separator with Selux AST System was determined to be substantially equivalent to the predicate device (K231536).

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.