LIAISON PLEX Gram-Negative Blood Culture Assay

K243013 · Luminex Corporation · PEN · Apr 18, 2025 · Microbiology

Device Facts

• Record ID: K243013
• Device Name: LIAISON PLEX Gram-Negative Blood Culture Assay
• Applicant: Luminex Corporation
• Product Code: PEN · Microbiology
• Decision Date: Apr 18, 2025
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 866.3365
• Device Class: Class 2

Intended Use

The LIAISON PLEX® Gram-Negative Blood Culture (BCN) Assay, performed using the automated, sample-to-result LIAISON PLEX® System, is a qualitative multiplexed in vitro diagnostic test for the simultaneous detection and identification of selected gram-negative pathogens and/or selected genetic determinants associated with antimicrobial resistance in positive blood culture bottles. LIAISON PLEX® BCN Assay is performed directly on blood culture media using blood culture bottles identified as positive by a continuous monitoring blood culture system which contain gram-negative bacteria as determined by Gram stain. The LIAISON PLEX® BCN Assay detects and identifies the following: Resistance Markers: CTX-M (blaCTX-M), IMP (blaIMP), KPC (blaKPC), NDM (blaNDM), OXA (blaOXA), VIM (blaVIM), MCR, SME (blaSME). Gram Negative Genera and Species: Enterobacteriaceae / Morganellaceae, Acinetobacter baumannii, Acinetobacter spp., Citrobacter spp., Enterobacter spp. (1), Escherichia coli (2), Haemophilus influenzae, Klebsiella oxytoca, Klebsiella pneumoniae, Klebsiella variicola, Morganella morganii, Neisseria meningitidis, Proteus spp., Pseudomonas aeruginosa, Pseudomonas spp., Salmonella spp., Serratia marcescens, Stenotrophomonas maltophilia. (1) Due to reclassification, Klebsiella aerogenes will be reported Enterobacter spp. (2) LIAISON PLEX® BCN Assay will not distinguish between Escherichia coli and Shigella spp. (S. dysenteriae, S. boydii, S. flexneri and S. sonnei). LIAISON PLEX® BCN Assay contains targets for the detection of genetic determinants associated with resistance to carbapenems (blaCTX-M, blaIMP, blaKPC, blaNDM, blaOXA48-like, blaVIM, blaSME) to aid in the identification of potentially antimicrobial-resistant organisms in positive blood culture samples. In addition, the panel includes an assay for the detection of the mobilized genetic determinant MCR, an emerging marker of public health importance. The antimicrobial resistance gene or marker detected may or may not be associated with the agent responsible for disease. Negative results for these select antimicrobial resistance gene and marker assays do not indicate susceptibility, as multiple mechanisms of resistance to β-lactams and colistin exist. LIAISON PLEX® BCN Assay is indicated for use in conjunction with other clinical and laboratory findings to aid in the diagnosis of bacterial bloodstream infections (BSI). LIAISON PLEX® BCN Assay is not intended to monitor treatment of these infections. Sub-culturing of positive blood cultures is necessary to recover organisms for antimicrobial susceptibility testing (AST), for identification of organisms not detected by LIAISON PLEX® BCN Assay, to detect mixed infections that may not be detected by LIAISON PLEX® BCN Assay, for association of antimicrobial resistance marker genes to a specific organism, or for epidemiological typing.

Device Story

The LIAISON PLEX® BCN Assay is an automated, sample-to-result, in vitro diagnostic test performed on the LIAISON PLEX® System. It uses a single-use disposable cartridge to process positive blood culture samples. The system performs mechanical and chemical cell lysis, magnetic bead-based nucleic acid isolation, and microarray-based hybridization. Target-specific capture DNA on a microarray binds extracted nucleic acids, followed by hybridization with mediator and gold nanoparticle probes. Silver enhancement of these probes allows for light scatter measurement to determine the presence or absence of specific gram-negative pathogens and resistance markers. The device is used in clinical laboratories by trained personnel. Results are provided to healthcare providers to aid in the diagnosis of bacterial bloodstream infections. The output helps clinicians identify potential antimicrobial-resistant organisms, though sub-culturing remains necessary for definitive AST and epidemiological typing. The device benefits patients by providing rapid identification of pathogens and resistance markers, potentially enabling earlier targeted therapy.

Clinical Evidence

Clinical performance was evaluated using 582 clinical specimens (351 prospective, 231 pre-selected) and 746 contrived specimens. The study compared the LIAISON PLEX® BCN Assay against a reference method algorithm (culture/VITEK 2/PCR/BDS). Combined prospective and pre-selected sensitivity/PPA ranged from 33.3% to 100% across targets, with specificity/NPA generally >99%. Contrived specimen sensitivity/PPA was 97.2%-100% and specificity/NPA was 99.6%-100%. The testing success rate was 99.7% for clinical and 99.9% for contrived samples.

Technological Characteristics

The device is a fully automated, bench-top system using a single-use disposable cartridge. It utilizes mechanical/chemical cell lysis, magnetic bead-based nucleic acid isolation, and microarray-based hybridization with gold nanoparticle probes and silver enhancement. It is a non-amplified, direct detection test. Connectivity is integrated into the LIAISON PLEX® System. It is designed for professional use in clinical laboratories.

Indications for Use

Indicated for use in patients with suspected bacterial bloodstream infections (BSI) to aid in the diagnosis by detecting gram-negative pathogens and antimicrobial resistance markers directly from positive blood culture bottles containing gram-negative bacteria (Gram stain confirmed). Not for treatment monitoring.

Regulatory Classification

Identification

A multiplex nucleic acid assay for identification of microorganisms and resistance markers from positive blood cultures is a qualitative in vitro device intended to simultaneously detect and identify microorganism nucleic acids from blood cultures that test positive by Gram stain or other microbiological stains. The device detects specific nucleic acid sequences for microorganism identification as well as for antimicrobial resistance. This device aids in the diagnosis of bloodstream infections when used in conjunction with other clinical and laboratory findings. However, the device does not replace traditional methods for culture and susceptibility testing.

Special Controls

In combination with the general controls of the FD&C Act, the Verigene® Gram Positive Blood Culture Nucleic Acid Test is subject to the following special controls: The special controls for the BC-GP Assay are contained in the guideline document entitled "Class II Special Controls Guideline: Multiplex Nucleic Acid Assay for Identification of Microorganisms and Resistance Markers from Positive Blood Cultures."

*Classification.* Class II (special controls). The special control for this device is FDA's guideline document entitled “Class II Special Controls Guideline: Multiplex Nucleic Acid Assay for Identification of Microorganisms and Resistance Markers from Positive Blood Cultures.” For availability of the guideline document, see § 866.1(e).

Predicate Devices

• VERIGENE Blood Culture Gram-Negative (BC-GN) Nucleic Acid Test (K132843)

Submission Summary (Full Text)

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FDA U.S. FOOD & DRUG ADMINISTRATION

April 18, 2025

Luminex Corporation
Sheri Calderon
Senior Regulatory Affairs Associate
4088 Commercial Avenue
Northbrook, Illinois 60062

Re: K243013
Trade/Device Name: LIAISON PLEX Gram-Negative Blood Culture Assay
Regulation Number: 21 CFR 866.3365
Regulation Name: Multiplex Nucleic Acid Assay For Identification Of Microorganisms And Resistance Markers From Positive Blood Cultures
Regulatory Class: Class II
Product Code: PEN, NSU
Dated: March 21, 2025
Received: March 21, 2025

Dear Sheri Calderon:

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

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

U.S. Food & Drug Administration
10903 New Hampshire Avenue
Silver Spring, MD 20993
www.fda.gov

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K243013 - Sheri Calderon
Page 2

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).

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 QS regulation requires device manufacturers to review and approve changes to device design and production (21 CFR 820.30 and 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 (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-safety-reporting-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.

All medical devices, including Class I and unclassified devices and combination product device constituent parts are required to be in compliance with the final Unique Device Identification System rule ("UDI Rule"). The UDI Rule requires, among other things, that a device bear a unique device identifier (UDI) on its label and package (21 CFR 801.20(a)) unless an exception or alternative applies (21 CFR 801.20(b)) and that the dates on the device label be formatted in accordance with 21 CFR 801.18. The UDI Rule (21 CFR 830.300(a) and 830.320(b)) also requires that certain information be submitted to the Global Unique Device Identification Database (GUDID) (21 CFR Part 830 Subpart E). For additional information on these requirements, please see the UDI System webpage at https://www.fda.gov/medical-devices/device-advice-comprehensive-regulatory-assistance/unique-device-identification-system-udi-system.

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-devices/medical-device-safety/medical-device-reporting-mdr-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/medical-devices/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-devices/device-advice-comprehensive-regulatory-

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K243013 - Sheri Calderon
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assistance/contact-us-division-industry-and-consumer-education-dice) for more information or contact DICE by email ([e-mail]) or phone [phone] or 301-796-7100).

Sincerely,

Noel J. Gerald -S

Noel J. Gerald, Ph.D.
Deputy Division Director
Division of Microbiology Devices
OHT7: Office of In Vitro Diagnostics
Office of Product Evaluation and Quality
Center for Devices and Radiological Health

Enclosure

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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
Indications for Use
Form Approved: OMB No. 0910-0120
Expiration Date: 07/31/2026
See PRA Statement below.

510(k) Number (if known)
K243013

Device Name
LIAISON PLEX® Gram-Negative Blood Culture Assay

Indications for Use (Describe)
The LIAISON PLEX® Gram-Negative Blood Culture (BCN) Assay, performed using the automated, sample-to-result LIAISON PLEX® System, is a qualitative multiplexed in vitro diagnostic test for the simultaneous detection and identification of selected gram-negative pathogens and/or selected genetic determinants associated with antimicrobial resistance in positive blood culture bottles. LIAISON PLEX® BCN Assay is performed directly on blood culture media using blood culture bottles identified as positive by a continuous monitoring blood culture system which contain gram-negative bacteria as determined by Gram stain.

The LIAISON PLEX® BCN Assay detects and identifies the following:

Resistance Markers:
CTX-M (blaCTX-M)
IMP (blaIMP)
KPC (blaKPC)
NDM (blaNDM)
OXA (blaOXA)
VIM (blaVIM)
MCR
SME (blaSME)

Gram Negative Genera and Species:
Enterobacteriaceae / Morganellaceae
Acinetobacter baumannii
Acinetobacter spp.
Citrobacter spp.
Enterobacter spp. (1)
Escherichia coli (2)
Haemophilus influenzae
Klebsiella oxytoca
Klebsiella pneumoniae
Klebsiella variicola
Morganella morganii
Neisseria meningitidis
Proteus spp.
Pseudomonas aeruginosa
Pseudomonas spp.
Salmonella spp.
Serratia marcescens
Stenotrophomonas maltophilia

(1) Due to reclassification, Klebsiella aerogenes will be reported Enterobacter spp.
(2) LIAISON PLEX® BCN Assay will not distinguish between Escherichia coli and Shigella spp. (S. dysenteriae, S. boydii, S. flexneri and S. sonnei)

LIAISON PLEX® BCN Assay contains targets for the detection of genetic determinants associated with resistance to

FORM FDA 3881 (8/23)
Page 1 of 2
PSC Publishing Services [phone]

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carbapenems (blaCTX-M, blaIMP, blaKPC, blaNDM, blaOXA48-like, blaVIM, blaSME) to aid in the identification of potentially antimicrobial-resistant organisms in positive blood culture samples. In addition, the panel includes an assay for the detection of the mobilized genetic determinant MCR, an emerging marker of public health importance. The antimicrobial resistance gene or marker detected may or may not be associated with the agent responsible for disease. Negative results for these select antimicrobial resistance gene and marker assays do not indicate susceptibility, as multiple mechanisms of resistance to $\beta$-lactams and colistin exist.

LIAISON PLEX® BCN Assay is indicated for use in conjunction with other clinical and laboratory findings to aid in the diagnosis of bacterial bloodstream infections (BSI). LIAISON PLEX® BCN Assay is not intended to monitor treatment of these infections. Sub-culturing of positive blood cultures is necessary to recover organisms for antimicrobial susceptibility testing (AST), for identification of organisms not detected by LIAISON PLEX® BCN Assay, to detect mixed infections that may not be detected by LIAISON PLEX® BCN Assay, for association of antimicrobial resistance marker genes to a specific organism, or for epidemiological typing.

Type of Use (Select one or both, as applicable)
☑ Prescription Use (Part 21 CFR 801 Subpart D)
☐ Over-The-Counter Use (21 CFR 801 Subpart C)

# CONTINUE ON A SEPARATE PAGE IF NEEDED.

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

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FORM FDA 3881 (8/23)
Page 2 of 2
PSC Publishing Services [phone]

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Diasorin

LIAISON PLEX® Gram-Negative Blood Culture Assay Traditional 510(k)

# 510(k) Summary

This Summary of 510(k) safety and effectiveness information is being submitted in accordance with the requirements of 21 CFR 807.92.

Preparation date: 16 April 2025

A. 510(k) Number:

K243013

B. Purpose for Submission:

Traditional 510(k), New Device

C. Measurand:

Nucleic acid sequences for the following organisms: Enterobacteriaceae / Morganellaceae, Acinetobacter baumannii, Acinetobacter spp., Citrobacter spp., Enterobacter spp., Escherichia coli, Haemophilus influenzae, Klebsiella oxytoca, Klebsiella pneumoniae, Klebsiella variicola, Morganella morganii, Neisseria meningitidis, Proteus spp., Pseudomonas aeruginosa, Pseudomonas spp., Salmonella spp., Serratia marcescens, and Stenotrophomonas maltophilia. Nucleic acid sequences for the following resistance markers: CTX-M (blaCTX-M), IMP (blaIMP), KPC (blaKPC), NDM (blaNDM), OXA (blaOXA), VIM (blaVIM), MCR, and SME (blaSME).

D. Type of Test:

Qualitative Multiplexed Direct Detection Hybridization Assay

E. Applicant:

Sheri Calderon, Luminex Corporation

4088 Commercial Avenue

Northbrook, IL 60062

[phone]

F. Proprietary and Established Names:

LIAISON PLEX® Gram-Negative Blood Culture Assay

G. Regulatory Information:

| Product Code | Classification | Regulation Section | Panel |
| --- | --- | --- | --- |
| PEN | II | 21 CFR 866.3365 – Multiplex Nucleic Acid Assay for Identification of Microorganisms and Resistance Markers from Positive Blood Cultures | 83 (Microbiology) |

Confidential & Restricted

510(k) Summary

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Diasorin

LIAISON PLEX® Gram-Negative Blood Culture Assay Traditional 510(k)

## H. Intended Use:

### 1. Intended use(s):

The LIAISON PLEX® Gram-Negative Blood Culture (BCN) Assay, performed using the automated, sample-to-result LIAISON PLEX® System, is a qualitative multiplexed in vitro diagnostic test for the simultaneous detection and identification of selected gram-negative pathogens and/or selected genetic determinants associated with antimicrobial resistance in positive blood culture bottles. LIAISON PLEX® BCN Assay is performed directly on blood culture media using blood culture bottles identified as positive by a continuous monitoring blood culture system which contain gram-negative bacteria as determined by Gram stain.

The LIAISON PLEX® BCN Assay detects and identifies the following:

| Resistance Markers | Gram Negative Genera and Species |
| --- | --- |
| CTX-M (blaCTX-M) | Enterobacteriaceae / Morganellaceae |
| IMP (blaIMP) | Acinetobacter baumannii |
| KPC (blaKPC) | Acinetobacter spp. |
| NDM (blaNDM) | Citrobacter spp. |
| OXA (blaOXA) | Enterobacter spp.¹ |
| VIM (blaVIM) | Escherichia coli² |
| MCR | Haemophilus influenzae |
| SME (blaSME) | Klebsiella oxytoca |
| | Klebsiella pneumoniae |
| | Klebsiella variicola |
| | Morganella morganii |
| | Neisseria meningitidis |
| | Proteus spp. |
| | Pseudomonas aeruginosa |
| | Pseudomonas spp. |
| | Salmonella spp. |
| | Serratia marcescens |
| | Stenotrophomonas maltophilia |

¹ Due to reclassification, Klebsiella aerogenes will be reported Enterobacter spp.
² LIAISON PLEX BCN Assay will not distinguish between Escherichia coli and Shigella spp. (S. dysenteriae, S. boydii, S. flexneri and S. sonnei)

LIAISON PLEX® BCN Assay contains targets for the detection of genetic determinants associated with resistance to carbapenems (blaCTX-M, blaIMP, blaKPC, blaNDM, blaOXA48-like, blaVIM, blaSME) to aid in the identification of potentially antimicrobial-resistant organisms in positive blood culture samples. In addition, the panel includes an assay for the detection of the mobilized genetic determinant MCR, an emerging marker of public health importance. The antimicrobial resistance gene or marker detected may or may not be associated with the agent responsible for disease. Negative results for these select antimicrobial resistance gene and marker assays do not indicate susceptibility, as multiple mechanisms of resistance to β-lactams and colistin exist.

LIAISON PLEX® BCN Assay is indicated for use in conjunction with other clinical and laboratory

Confidential & Restricted

510(k) Summary

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Diasorin

LIAISON PLEX® Gram-Negative Blood Culture Assay Traditional 510(k)

findings to aid in the diagnosis of bacterial bloodstream infections (BSI). LIAISON PLEX® BCN Assay is not intended to monitor treatment of these infections. Sub-culturing of positive blood cultures is necessary to recover organisms for antimicrobial susceptibility testing (AST), for identification of organisms not detected by LIAISON PLEX® BCN Assay, to detect mixed infections that may not be detected by LIAISON PLEX® BCN Assay, for association of antimicrobial resistance marker genes to a specific organism, or for epidemiological typing.

2. Indication(s) for use:
Same as intended use.

3. Special conditions for use statement(s):
For prescription use only.
For in vitro diagnostic use only.

4. Special instrument requirements:
For use with LIAISON PLEX® Systems.

I. Device Description:
The LIAISON PLEX® Gram-Negative Blood Culture (BCN) Assay is an automated test for the detection and identification of nucleic acid from gram-negative bacteria in a positive blood culture media sample. The BCN Assay is performed directly on blood culture media using blood culture bottles identified as positive by a continuous monitoring blood culture system, and which contain gram-negative bacteria, as determined by a Gram stain.

The LIAISON PLEX® System is a fully automated, bench-top "sample-to-answer" device that performs sample preparation, polymerase chain reaction (PCR) and microarray-based hybridization for the detection of target-specific nucleic acids. The test reagents are supplied as a single, disposable test cartridge. PCR is not performed on the LIAISON PLEX® BCN Assay, as it is a non-amplified, direct detection test performed on the LIAISON PLEX® System.

J. Substantial Equivalence Information:

1. Predicate device name(s):
VERIGENE Blood Culture Gram-Negative (BC-GN) Nucleic Acid Test

2. Predicate 510(k) number(s):
K132843

3. Comparison with predicate:
The following tables compare the LIAISON PLEX® Gram-Negative Blood Culture Assay to the VERIGENE Gram-Negative Blood Culture (BC-GN) Nucleic Acid Test.

Confidential & Restricted

510(k) Summary

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Diasorin

LIAISON PLEX® Gram-Negative Blood Culture Assay Traditional 510(k)

| Comparison to Predicate Device | Predicate Device: K132843
VERIGENE Gram-Negative Blood Culture (BC-GN) Nucleic Acid Test, K132843 | Candidate Device: K243013
LIAISON PLEX® Gram-Negative Blood Culture Assay |
| --- | --- | --- |
| Product Code | PEN | PEN |
| Regulation Number | 21 CFR 866.3365 | 21 CFR 866.3365 |
| Organism Detected | Organisms: Acinetobacter spp.,
Citrobacter spp., Enterobacter spp.,
Proteus spp., Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca, and Pseudomonas aeruginosa

Resistance Markers: CTX-M (blaCTX-M), KPC (blaKPC), NDM (blaNDM), VIM (blaVIM), IMP (blaIMP), and OXA (blaOXA) | Organisms: Enterobacteriaceae / Morganellaceae, Acinetobacter baumannii, Acinetobacter spp.,
Citrobacter spp., Enterobacter spp., Escherichia coli, Haemophilus influenzae, Klebsiella oxytoca, Klebsiella pneumoniae, Klebsiella variicola, Morganella morganii, Neisseria meningitidis, Proteus spp., Pseudomonas aeruginosa, Pseudomonas spp., Salmonella spp., Serratia marcescens, and Stenotrophomonas maltophilia

Resistance markers: CTX-M (blaCTX-M), IMP (blaIMP), KPC (blaKPC), NDM (blaNDM), OXA (blaOXA), VIM (blaVIM), MCR, and SME (blaSME). |
| Measurand | Nucleic acid from Organisms detected | Same |
| Intended Use | The Verigene® Gram Negative Blood Culture Nucleic Acid Test (BC-GN), performed using the sample-to-result Verigene System, is a qualitative multiplexed in vitro diagnostic test for the simultaneous detection and identification of selected gram-negative bacteria and resistance markers. BC-GN is performed directly on blood culture media using blood culture bottles identified as positive by a continuous monitoring blood culture system and which contain gram-negative bacteria as determined by gram stain.

BC-GN detects and identifies the following:

**Bacterial Genera and Species**
Acinetobacter spp.
Citrobacter spp.
Enterobacter spp.
Proteus spp.
Escherichia coli^{1}
Klebsiella pneumoniae
Klebsiella oxytoca
Pseudomonas aeruginosa

**Resistance Markers**
CTX-M (blaCTX-M)
KPC (blaKPC)
NDM (blaNDM)
VIM (blaVIM)
IMP (blaIMP) | The LIAISON PLEX® Gram-Negative Blood Culture (BCN) Assay, performed using the automated, sample-to-result LIAISON PLEX® System, is a qualitative multiplexed in vitro diagnostic test for the simultaneous detection and identification of selected gram-negative pathogens and/or selected genetic determinants associated with antimicrobial resistance in positive blood culture bottles. BCN is performed directly on blood culture media using blood culture bottles identified as positive by a continuous monitoring blood culture system and which contain gram-negative bacteria as determined by Gram stain.

The BCN Assay detects and identifies the following:

**Gram Negative Genera and Species**
Enterobacteriaceae / Morganellaceae
Acinetobacter baumannii
Acinetobacter spp.
Citrobacter spp.
Enterobacter spp.^{1}
Escherichia coli^{2}
Haemophilus influenzae
Klebsiella oxytoca
Klebsiella pneumoniae
Klebsiella variicola |

Confidential & Restricted

510(k) Summary

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Diasorin

LIAISON PLEX® Gram-Negative Blood Culture Assay Traditional 510(k)

| Comparison to Predicate Device | Predicate Device: K132843
VERIGENE Gram-Negative Blood Culture (BC-GN) Nucleic Acid Test, K132843 | Candidate Device: K243013
LIAISON PLEX® Gram-Negative Blood Culture Assay |
| --- | --- | --- |
| | OXA (blaOXA) | Morganella morganii
Neisseria meningitidis
Proteus spp.
Pseudomonas aeruginosa
Pseudomonas spp.
Salmonella spp.
Serratia marcescens
Stenotrophomonas maltophilia |
| | ¹BC-GN will not distinguish Escherichia coli from Shigella spp. (S. dysenteriae, S. flexneri, S. boydii, and S. sonnei)

BC-GN is indicated for use in conjunction with other clinical and laboratory findings to aid in the diagnosis of bacterial bloodstream infections; however, it is not used to monitor these infections. Sub-culturing of positive blood cultures is necessary to recover organisms for antimicrobial susceptibility testing (AST), for identification of organisms not detected by BC-GN, to detect mixed infections that may not be detected by BC-GN, for association of antimicrobial resistance marker genes to a specific organism, or for epidemiological typing. | Resistance Markers
CTX-M (blaCTX-M)
IMP (blaIMP)
KPC (blaKPC)
NDM (blaNDM)
OXA (blaOXA)
VIM (blaVIM)
MCR
SME (blaSME)

¹ Due to reclassification, Klebsiella aerogenes will be reported Enterobacter spp.
² LIAISON PLEX BCN will not distinguish between Escherichia coli and Shigella spp. (S. dysenteriae, S. boydii, S. flexneri and S. sonnei)

LIAISON PLEX® BCN Assay contains targets for the detection of genetic determinants associated with resistance to carbapenems (blaCTX-M, blaIMP, blaKPC, blaNDM, blaOXA48-like, blaVIM, blaSME) to aid in the identification of potentially antimicrobial-resistant organisms in positive blood culture samples. In addition, the panel includes an assay for the detection of the mobilized genetic determinant MCR, an emerging marker of public health importance. The antimicrobial resistance gene or marker detected may or may not be associated with the agent responsible for disease. Negative results for these select antimicrobial resistance gene and marker assays do not indicate susceptibility, as multiple mechanisms of resistance to β-lactams and colistin exist.

LIAISON PLEX® BCN Assay is indicated for use in conjunction with other clinical and laboratory findings to aid in the diagnosis of bacterial bloodstream infections (BSI). LIAISON PLEX® BCN Assay is not intended to monitor treatment of these infections. |

Confidential & Restricted

510(k) Summary

Page 5 of 47

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Diasorin

LIAISON PLEX® Gram-Negative Blood Culture Assay Traditional 510(k)

| Comparison to Predicate Device | Predicate Device: K132843
VERIGENE Gram-Negative Blood Culture (BC-GN) Nucleic Acid Test, K132843 | Candidate Device: K243013
LIAISON PLEX® Gram-Negative Blood Culture Assay |
| --- | --- | --- |
| | | Sub-culturing of positive blood cultures is necessary to recover organisms for antimicrobial susceptibility testing (AST), for identification of organisms not detected by LIAISON PLEX® BCN Assay, to detect mixed infections that may not be detected by LIAISON PLEX® BCN Assay, for association of antimicrobial resistance marker genes to a specific organism, or for epidemiological typing. |
| Automated System (Sample to Answer) | Automated | Same |
| Instrumentation | VERIGENE | LIAISON PLEX |
| Sample Types | Positive Blood Culture | Same |

Confidential & Restricted

510(k) Summary

Page 6 of 47

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Diasorin

LIAISON PLEX® Gram-Negative Blood Culture Assay Traditional 510(k)

# K. Standards/Guidance Documents Referenced:

- Class II Special Controls Guideline: Multiplex Nucleic Acid Assay for Identification of Microorganisms and Resistance Markers from Positive Blood Cultures (May 2015)
- Electronic Submission Template for Medical Device 510(k) Submissions - Guidance for Industry and Food and Drug Administration Staff (October 2, 2023).
- Content of Premarket Submissions for Device Software Functions - Guidance for Industry and Food and Drug Administration Staff (June 14, 2023).
- Cybersecurity in Medical Devices: Quality System Considerations and Content of Premarket Submissions - Guidance for Industry and Food and Drug Administration Staff (September 23, 2023).
- Statistical Guidance on Reporting Results from Studies Evaluating Diagnostic Tests - Guidance for Industry and FDA Staff (March 13, 2007).
- CLSI. User Protocol for Evaluation of Qualitative Test Performance; Approved Guideline - Second Edition. CLSI document EP12-A2. Wayne, PA: Clinical and Laboratory Standards Institute; 2008.
- CLSI. Evaluation of Stability of In Vitro Diagnostic Reagents; Approved Guideline. CLSI document EP25-A. Wayne, PA: Clinical and Laboratory Standards Institute; 2009.
- ISO 14971:2019 Medical devices - Application of risk management to medical devices
- IEC 62366-1:2015 +A1:2020 Medical devices - Part 1: Application of usability engineering to medical devices
- ISO 62304:2006 Medical device software - Software life-cycle processes
- ISO 15223-1:2021: Medical Devices - Symbols to be used with medical device labels, labeling and information to be supplied - Part 1: General requirements
- IEC 61010-1 Ed. 3.1 2017-01: Safety requirements for electrical equipment for measurement, control, and laboratory use - Part 1: General requirements
- EN 61010-2-101:2002/IEC 61010-2-101:2015: Safety requirements for electrical equipment for measurement, control and laboratory use - Part 2-101: Particular requirements for in vitro diagnostic (IVD) medical equipment.
- IEC 60601-1-2:2014 (Edition 4.0): Medical electrical equipment - Part 1-2: General requirements for basic safety and essential performance - Collateral Standard: Electromagnetic disturbances - Requirements and tests
- ISO 13485:2016/EN ISO 13485:2016; Medical devices - Quality Management System - Requirements for regulatory purposes
- ISO 20916:2019; In vitro diagnostic medical devices. Clinical performance studies using specimens from human subjects. Good study practice
- EN ISO 18113-1:2011; In vitro diagnostic medical devices - Information supplied by the manufacturer (labeling). Terms, definition and general requirements
- EN ISO 18113-2:2011; In vitro diagnostic medical devices - Information supplied by the manufacturer (labeling) - Part 2: In vitro diagnostic reagents for professional use

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- EN ISO 18113-3:2011; In vitro diagnostic medical devices - Information supplied by the manufacturer (labeling) – Part 3: In vitro diagnostic instruments for professional use
- EN ISO 23640:2015; In vitro diagnostic medical devices - Evaluation of stability of in vitro diagnostic reagents
- IEC 61326-1:2012; Electrical equipment for measurement control and laboratory use - EMC requirements - Part 1: General requirements
- EN 61326-2-6:2006/IEC 61326-2-6:2012; Electrical equipment for measurement control and laboratory use - EMC requirements - Part 2-6: Particular requirements - In vitro diagnostic (IVD) medical equipment

## L. Test Principle:

The LIAISON PLEX® Gram-Negative Blood Culture (BCN) Assay is performed directly on blood culture media using blood culture bottles identified as positive by a continuous monitoring blood culture system, and which contain gram-negative bacteria, as determined by a Gram stain. The system consists of an instrument and a single-use, disposable test cartridge. The user loads an aliquot of the sample into the sample port of the LIAISON PLEX® Gram-Negative Blood Culture Assay Cartridge. Next, the user sets up the sample order on the LIAISON PLEX® System by first entering the sample information or scanning the barcode ID located on the sample tube, then scanning the barcode ID located on the test cartridge. Last, the user inserts the test cartridge into the processing module to initiate the test. The LIAISON PLEX® System identifies the assay being run and automatically initiates the proper testing protocol to process the sample, analyze the data, and generate test results.

The LIAISON PLEX® System automates the LIAISON PLEX® BCN Assay sample analysis through the following steps: a) Sample Preparation: Nucleic acid extraction via mechanical and chemical cell lysis and magnetic bead-based nucleic acid isolation; b) Hybridization: Extracted nucleic acid hybridize to target-specific capture DNA on a microarray format, and target-specific mediator and gold nanoparticle probe hybridize to captured nucleic acids; c) Signal Analysis: Gold nanoparticle probes bound specifically to target-containing spots in the microarray are silver-enhanced, and light scatter from the spots is measured and further analyzed to determine the presence (Detected) or absence (Not Detected) of a target.

## M. Performance Characteristics:

### 1. Analytical performance:

#### a. Precision/Reproducibility:

**Site-to-site Reproducibility**

Site-to-site reproducibility of the LIAISON PLEX® BCN Assay was evaluated by testing LIAISON PLEX® BCN Assay cartridges with a reproducibility panel, blinded to operators, consisting of eight blood culture samples; six representative on-panel organisms

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(Acinetobacter baumannii, Klebsiella pneumoniae, Haemophilus influenzae, Neisseria meningitidis, Escherichia coli, and Serratia marcescens) individually cultured at ring positivity and eight hours after ring positivity, one negative sample contrived with an off-panel organism (Staphylococcus aureus), and one negative blood culture matrix (NBM) sample. Each sample of the blinded reproducibility panel was tested in triplicate for each sample type by two operators at three sites, two external and one internal, for five non-consecutive testing days. The call agreement results (%) are presented in Table 1, which demonstrated 100% call accuracy for ring positive, ring positive plus 8 hours, and negative blood matrix samples, and 99.4% call accuracy for the contrived negative sample (Staphylococcus aureus). Overall, results of site-to-site reproducibility evaluation demonstrated 99.9% reproducibility of the LIAISON PLEX® BCN Assay.

Table 1. LIAISON PLEX® Gram-Negative Blood Culture Assay Site-to-Site Reproducibility Results Summary

| Organism ID | Reportable Targets | Sample Type | Call Agreement (%) with Expected Results | Overall 95% C.I. |
| --- | --- | --- | --- | --- |
| Site 1 | Site 2 | Site 3 | Overall (All Sites) |
| Acinetobacter baumannii | Acinetobacter baumannii | Acinetobacter spp. | Ring Positive | 100% (30/30) | 100% (30/30) | 100% (30/30) | 100% (90/90) | 95.9% - 100% |
| Ring Positive + 8 HR | 100% (30/30) | 100% (30/30) | 100% (30/30) | 100% (90/90) | 95.9% - 100% |
| Klebsiella pneumoniae | Enterobacteria ceae / Morganellaceae | Klebsiella pneumoniae | Ring Positive | 100% (30/30) | 100% (31/31) | 100% (30/30) | 100% (91/91) | 95.9% - 100% |
| Ring Positive + 8 HR | 100% (30/30) | 100% (30/30) | 100% (30/30) | 100% (90/90) | 95.9% - 100% |
| Haemophilus influenzae | Haemophilus influenzae | Ring Positive | 100% (30/30) | 100% (30/30) | 100% (30/30) | 100% (90/90) | 95.9% - 100% |
| Ring Positive + 8 HR | 100% (30/30) | 100% (30/30) | 100% (30/30) | 100% (90/90) | 95.9% - 100% |
| Neisseria meningitidis | Neisseria meningitidis | Ring Positive | 100% (30/30) | 100% (30/30) | 100% (30/30) | 100% (90/90) | 95.9% - 100% |
| Ring Positive + 8 HR | 100% (30/30) | 100% (30/30) | 100% (30/30) | 100% (90/90) | 95.9% - 100% |
| Escherichia coli | Enterobacteria ceae / Morganellaceae | Escherichia coli | Ring Positive | 100% (30/30) | 100% (30/30) | 100% (30/30) | 100% (90/90) | 95.9% - 100% |
| Ring Positive + 8 HR | 100% (30/30) | 100% (30/30) | 100% (30/30) | 100% (90/90) | 95.9% - 100% |
| Serratia marcescens | Enterobacteria ceae / Morganellaceae | Serratia marcescens | Ring Positive | 100% (30/30) | 100% (30/30) | 100% (30/30) | 100% (90/90) | 95.9% - 100% |
| Ring Positive + 8 HR | 100% (30/30) | 100% (30/30) | 100% (30/30) | 100% (90/90) | 95.9% - 100% |

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| Organism ID | Reportable Targets | Sample Type | Call Agreement (%) with Expected Results | | | | Overall 95% C.I. |
| --- | --- | --- | --- | --- | --- | --- | --- |
| | | | Site 1 | Site 2 | Site 3 | Overall (All Sites) | |
| Staphylococcus aureus | None | Ring Positive + 8 HR | 98.3% (59/60) | 100% (60/60) | 100% (60/60) | 99.4% (179/180) | 96.9% - 99.9% |
| No Target (Negative Blood Matrix) | None | Ring Negative | 100% (60/60) | 100% (60/60) | 100% (60/60) | 100% (180/180) | 97.9% - 100% |
| Resistance Markers | | | | | | | |
| Acinetobacter baumannii | OXA | Ring Positive | 100% (30/30) | 100% (30/30) | 100% (30/30) | 100% (90/90) | 95.9% - 100% |
| | | Ring Positive + 8 HR | 100% (30/30) | 100% (30/30) | 100% (30/30) | 100% (90/90) | 95.9% - 100% |
| Klebsiella pneumoniae | KPC | Ring Positive | 100% (30/30) | 100% (31/31) | 100% (30/30) | 100% (91/91) | 95.9% - 100% |
| | | Ring Positive + 8 HR | 100% (30/30) | 100% (30/30) | 100% (30/30) | 100% (90/90) | 95.9% - 100% |
| Escherichia coli | MCR | Ring Positive | 100% (30/30) | 100% (30/30) | 100% (30/30) | 100% (90/90) | 95.9% - 100% |
| | | Ring Positive + 8 HR | 100% (30/30) | 100% (30/30) | 100% (30/30) | 100% (90/90) | 95.9% - 100% |
| Serratia marcescens | SME | Ring Positive | 100% (30/30) | 100% (30/30) | 100% (30/30) | 100% (90/90) | 95.9% - 100% |
| | | Ring Positive + 8 HR | 100% (30/30) | 100% (30/30) | 100% (30/30) | 100% (90/90) | 95.9% - 100% |
| Overall Agreement (All Targets / Sample Types) | | | 99.8% (479/480) | 100% (481/481) | 100% (480/480) | 99.9% (1440/1441) | |
| Overall (All Sites) 95% Confidence Interval | | | | | | | 99.6% - 100% |

## Precision/Repeatability

Within laboratory (operator-to-operator) precision/repeatability of the LIAISON PLEX® BCN Assay was evaluated based on the results generated by two operators testing site-to-site reproducibility samples at ring positivity and at 8 hours plus ring positivity, contrived negative, and negative blood culture samples. Within laboratory precision/repeatability of the LIAISON PLEX® BCN Assay was 99.8%, and results are summarized in Table 2.

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Table 2. LIAISON PLEX® Gram-Negative Blood Culture Assay Within-Laboratory Precision/Repeatability Results Summary

| Organism | Target Type | Agreement with Expected Results | |
| --- | --- | --- | --- |
| | | Operator 1 | Operator 2 |
| Acinetobacter baumannii | Ring Positive | 100% 15/15 | 100% 15/15 |
| | Ring Positive +8 Hours | 100% 15/15 | 100% 15/15 |
| Klebsiella pneumoniae | Ring Positive | 100% 15/15 | 100% 15/15 |
| | Ring Positive +8 Hours | 100% 15/15 | 100% 15/15 |
| Haemophilus influenzae | Ring Positive | 100% 15/15 | 100% 15/15 |
| | Ring Positive +8 Hours | 100% 15/15 | 100% 15/15 |
| Neisseria meningitidis | Ring Positive | 100% 15/15 | 100% 15/15 |
| | Ring Positive +8 Hours | 100% 15/15 | 100% 15/15 |
| Escherichia coli | Ring Positive | 100% 15/15 | 100% 15/15 |
| | Ring Positive +8 Hours | 100% 15/15 | 100% 15/15 |
| Serratia marcescens | Ring Positive | 100% 15/15 | 100% 15/15 |
| | Ring Positive +8 Hours | 100% 15/15 | 100% 15/15 |
| Staphylococcus aureus | Off-panel Negative | 100% 30/30 | 96.7% 29/30 |
| No Target (Negative Blood Matrix) | Off-panel Negative | 100% 30/30 | 100% 30/30 |
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b. Linearity/assay reportable range:
Not applicable. The LIAISON® PLEX Gram-Negative Blood Culture Assay is a qualitative assay.

c. Traceability, Stability, Expected values (controls, calibrators, or methods):

Controls

Several controls are built into the assay and system to ensure identification of processing

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errors and to establish validity of test results.

## Internal Controls

Each LIAISON PLEX® Gram-Negative Blood Culture Assay cartridge includes internal controls to ensure performance of sample preparation and detection. The internal extraction control is present in the lysis tube when the sample is added. Sample preparation is initiated and the extraction control assesses extraction, nucleic acid recovery, and detection. Finally, addition of a post-extraction hybridization control serves as an indicator of successful hybridization. Internal control results are reported as Pass or Fail on the printed reports (see Table 3 for detailed explanations of each control result). Internal controls must generate a signal above threshold in each internal reaction for the system to report a valid test result.

Table 3. Interpretation of Controls on the LIAISON PLEX® Gram-Negative Blood Culture Assay Report

| Internal Control Result | Explanation | Suggested Action |
| --- | --- | --- |
| Pass | Test was completed and internal controls were successful, indicating that valid results were generated. | Review and report results |
| Fail | One or more internal control failed. | Repeat test with a new cartridge |

## External Controls

Positive and negative external controls should be tested with each new lot or shipment of reagents, or monthly, (whichever occurs first), or in accordance with updated local, regional, state, and/or federal guidelines. Verified negative blood matrix can be used as the negative control. Previously characterized positive samples or verified negative blood matrix spiked with well characterized organisms may be used as the external positive control. External controls should be used in accordance with laboratory protocols and in accordance with local, state, and federal accrediting organizations, as applicable.

## Stability

## Specimen Stability

Performance of the LIAISON PLEX® Gram-Negative Blood Culture (BCN) Assay was assessed using specimens tested in a fresh state (at bottle/ring positive and at bottle/ring positive + 8 hours) and after exposure to various storage conditions. Conditions tested included refrigerated storage (2° to 8°C) and room temperature storage (15°C to 30°C) to span the typical "fresh specimen" storage conditions across multiple time points. Positive specimens containing four target organisms representing a total of eight gram-negative targets and select resistance markers were tested as well as negative blood matrix control specimen containing no target organisms. All positives tested yielded 100% positivity across all time-points and storage conditions tested. The negative sample demonstrated 0% positivity across all time-points and storage conditions tested. The results demonstrated that specimens may be stored under the following temperature conditions

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without impacting the performance of the LIAISON PLEX® BCN cartridge:

- Up to 72 hours (3 days) at Refrigerated (2-8°C) or Room Temperature (15-30°C) storage conditions.

## Device Stability

A shelf-life study was conducted to evaluate the real-time stability of the LIAISON PLEX® BCN Assay at the recommended storage conditions of room temperature (15°C – 30°C). Real-time stability was assessed using seven Positive Control panels which interrogate all reportable targets in the assay, and one Negative Control which consisted of negative blood matrix. Results of real-time stability demonstrated the LIAISON PLEX BCN® Assay is stable for at least 3 months when stored at 15°C – 30°C. Shelf-life will be extended based upon results of on-going stability testing.

An open box stability study was performed to evaluate the stability of the LIAISON PLEX® BCN Assay cartridges at room temperature once removed from their foil pouch. Testing was performed shortly after kits were manufactured and will be repeated at the end of the product shelf-life. Non-aged (Tinitial) cartridges were tested at 0 hours (T0), 2 hours (T2), and 9 hours (T9) after removal from their pouch. Each time point included testing of seven Positive Control panels which interrogate all reportable targets in the assay, and one Negative Control which consisted of negative blood matrix. Results of open-box stability indicate the cartridges are stable for up to eight hours after cartridges are removed from their foil pouches and stored at room temperature.

## Fresh vs. Frozen Specimen Stability

A fresh vs. frozen specimen stability study was performed to evaluate the performance of the LIAISON PLEX® Blood Culture Negative (BCN) Assay across specimens that have been prepared "fresh" (at two growth durations referred to as Bottle/Ring Positive and Bottle/Ring Positive + 8 hours) and subjected to a range of freeze/thaw (F/T) cycles as well as those experiencing a prolonged storage in frozen conditions. The study was performed using four representative organisms detected by the LIAISON PLEX® BCN Assay cultured in blood culture bottles. Performance testing using negative blood matrix served as a control test during the study. Material was tested under 5 different conditions – Initial Testing: Fresh, 1st Freeze-thaw, 2nd Freeze-thaw; 1-Month Testing: 1st Freeze-thaw and 2nd Freeze-thaw. Material was frozen for a minimum of 8 hours in between each freeze-thaw cycle. In the 1-Month testing, material was frozen for at least 34 days prior to the 1st freeze-thaw. A total of 455 replicates were included in this study. The results demonstrated 100% positivity for target positive samples at both growth durations and all freeze-thaw conditions. The negative blood demonstrated 0% positivity of all reportable targets for the assay at all freeze-thaw conditions.

## d. Growth and Detection Study

The Growth and Detection study was performed to evaluate detection of species / targets listed in Table 4 in blood cultures. For the evaluation, 15 organisms representing all 26 reportable targets were tested at Ring Positive and Ring Positive + 8 hours. Concentrations

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for both conditions are outlined in Table 4. One negative blood bottle was also grown for at least five days in an automated blood culture system until it was flagged as “negative” and was also tested on the LIAISON PLEX® BCN Assay.

A minimum of three Bottle/Ring Positive and three Bottle/Ring Positive +8 Hour bottles from each BCN organism were tested in triplicate and one negative blood bottle was tested in triplicate on the LIAISON PLEX® BCN Assay. The LIAISON PLEX® BCN Assay results, presented in Table 4 and Table 5, demonstrated 100% positivity for target positive samples and 0% positivity when tested with negative blood.

Table 4 – Growth and Detection Summary – Positive Samples

| Positive Samples | | | | | | | |
| --- | --- | --- | --- | --- | --- | --- | --- |
| Species Tested | Targets Tested | At Positivity | | | 8 Hours After Positivity | | |
| | | Per Bottle (CFU/mL) | Mean (CFU/mL) | Positive Agreement /Total (% Detected) | Per Bottle (CFU/mL) | Mean (CFU/mL) | Positive Agreement /Total (% Detected) |
| Acinetobacter baumannii [OXA] IHMA 128307 | Acinetobacter baumannii / Acinetobacter spp. / OXA | 2.13E+08 | 2.06E+08 | 9/9 (100%) | 2.09E+08 | 1.63E+08 | 9/9 (100%) |
| | | 2.18E+08 | | | 1.06E+08 | | |
| | | 1.86E+08 | | | 1.75E+08 | | |
| Citrobacter freundii [VIM] IHMA 549813 | Citrobacter spp. / Enterobacteriaceae / Morganellaceae / VIM | 9.63E+08 | 1.28E+09 | 9/9 (100%) | 1.76E+09 | 1.87E+09 | 9/9 (100%) |
| | | 1.49E+09 | | | 2.16E+09 | | |
| | | 1.39E+09 | | | 1.68E+09 | | |
| Enterobacter cloacae ATCC 35030 | Enterobacter spp. / Enterobacteriaceae / Morganellaceae | 1.46E+09 | 1.58E+09 | 9/9 (100%) | 1.68E+09 | 2.04E+09 | 9/9 (100%) |
| | | 1.61E+09 | | | 2.07E+09 | | |
| | | 1.68E+09 | | | 2.36E+09 | | |
| Escherichia coli [MCR] NCTC 13846 | Enterobacteriaceae / Morganellaceae / Escherichia coli / MCR | 1.70E+09 | 1.87E+09 | 9/9 (100%) | 1.45E+09 | 1.65E+09 | 9/9 (100%) |
| | | 1.96E+09 | | | 1.83E+09 | | |
| | | 1.95E+09 | | | 1.66E+09 | | |
| Klebsiella oxytoca [CTX-M] IHMA 683079 | CTX-M / Enterobacteriaceae / Morganellaceae / Klebsiella oxytoca | 4.53E+08 | 9.69E+08 | 9/9 (100%) | 5.3E+08 | 3.41E+08 | 9/9 (100%) |
| | | 1.48E+09 | | | 2.9E+08 | | |
| | | 9.73E+08 | | | 2.04E+08 | | |
| Klebsiella pneumoniae [KPC] IHMA 629630 | Enterobacteriaceae / Morganellaceae / KPC / Klebsiella pneumoniae | 1.33E+09 | 1.56E+09 | 9/9 (100%) | 1.55E+09 | 1.58E+09 | 9/9 (100%) |
| | | 1.66E+09 | | | 1.61E+09 | | |
| | | 1.69E+09 | | | 1.59E+09 | | |
| Klebsiella variicola ATCC BAA-830 | Enterobacteriaceae / Morganellaceae / Klebsiella variicola | 1.66E+09 | 1.75E+09 | 9/9 (100%) | 2.00E+09 | 2.06E+09 | 9/9 (100%) |
| | | 1.82E+09 | | | 2.13E+09 | | |
| | | 1.78E+09 | | | 2.05E+09 | | |
| Salmonella ent ent Enteritidis ATCC 13076 | Enterobacteriaceae / Morganellaceae / Salmonella spp. | 4.90E+07 | 2.56E+08 | 9/9 (100%) | 1.88E+09 | 1.85E+09 | 9/9 (100%) |
| | | 1.38E+08 | | | 2.06E+09 | | |
| | | 5.80E+08 | | | 1.61E+09 | | |
| Serratia | Enterobacteriaceae / | 1.55E+08 | 2.38E+08 | 9/9 | 1.82E+09 | 1.47E+09 | 12/12^{1} |

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| Positive Samples | | | | | | | |
| --- | --- | --- | --- | --- | --- | --- | --- |
| Species Tested | Targets Tested | At Positivity | | | 8 Hours After Positivity | | |
| | | Per Bottle (CFU/mL) | Mean (CFU/mL) | Positive Agreement /Total (% Detected) | Per Bottle (CFU/mL) | Mean (CFU/mL) | Positive Agreement /Total (% Detected) |
| marcescens [SME] NCTC 13920 | Morganellaceae / SME / Serratia marcescens | 3.27E+08 | | (100%) | 1.39E+09 | | (100%) |
| | | 2.32E+08 | | | 1.19E+09 | | |
| Morganella morganii [NDM] IHMA 605873 | Enterobacteriaceae / Morganellaceae / Morganella morganii / NDM | 1.77E+09 | | 9/9 (100%) | 2.75E+09 | | 9/9 (100%) |
| | | 1.76E+09 | 1.68E+09 | | 2.65E+09 | 2.71E+09 | |
| | | 1.52E+09 | | | 2.74E+09 | | |
| Pseudomonas aeruginosa [IMP] IHMA 576602 | IMP / Pseudomonas aeruginosa / Pseudomonas spp. | 8.97E+08 | | 9/9 (100%) | 1.33E+09 | | 9/9 (100%) |
| | | 7.30E+08 | 7.99E+08 | | 1.14E+09 | 1.26E+09 | |
| | | 7.70E+08 | | | 1.30E+09 | | |
| Stenotrophomonas maltophilia ATCC 13636 | Stenotrophomonas maltophilia | 3.83E+08 | | 9/9 (100%) | 1.23E+09 | | 9/9 (100%) |
| | | 5.23E+08 | 4.48E+08 | | 9.47E+08 | 1.00E+09 | |
| | | 4.37E+08 | | | 8.27E+08 | | |
| Proteus mirabilis ATCC 12453 | Enterobacteriaceae / Morganellaceae / Proteus spp. | 2.14E+09 | | 9/9 (100%) | 2.28E+09 | | 9/9 (100%) |
| | | 2.35E+09 | 2.26E+09 | | 1.80E+09 | 2.12E+09 | |
| | | 2.30E+09 | | | 2.28E+09 | | |
| Haemophilus influenzae ATCC 9007 | Haemophilus influenzae | 2.12E+09 | | 9/9 (100%) | 1.37E+09 | | 9/9 (100%) |
| | | 2.32E+09 | 2.13E+09 | | 2.42E+09 | 1.70E+09 | |
| | | 1.96E+09 | | | 1.32E+09 | | |
| Neisseria meningitidis ATCC 43744 | Neisseria meningitidis | 2.39E+08 | | 9/9 (100%) | 1.43E+08 | | 9/9 (100%) |
| | | 2.36E+08 | 1.88E+08 | | 4.10E+08 | 2.87E+08 | |
| | | 8.93E+07 | | | 3.07E+08 | | |

¹One OXA false positive was observed in initial testing. An additional set of replicates was tested resulting in 12 total replicates.

Table 5 – Growth and Detection Summary – Negative Samples

| Negative Samples | | | | |
| --- | --- | --- | --- | --- |
| Species Tested | Targets Tested | Per Bottle (CFU/mL) | Mean (CFU/mL) | Targets Detected/Total (% Detected) |
| Negative Blood | None | 0.00E+00 | 0.00E+00 | 0/3 (0%) |

e. Analytical Reactivity (Inclusivity)

The analytical reactivity study was performed to evaluate the inclusivity of the LIAISON PLEX® BCN Assay through laboratory testing of multiple strains representing “on-panel” reportable target bacteria or bacterial species. All on-panel organisms (n = 246) were

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tested in triplicate. One hundred percent (100%) positivity was noted for all targets including expected resistance marker calls for 245 of the 246 on-panel organisms. A summary of organism results is listed in Table 6 and a summary of resistance marker results is listed in Table 7. Of the 246 on-panel organisms tested, 17 organisms generated additional target calls that align with known cross-reactivity based on in silico analysis, or design features. Additionally, one on-panel organism (S. proteamaculans) only generated the known cross-reactivity target call, not the expected target call. The 18 cross-reactive organisms are highlighted in Table 8.

Table 6: LIAISON PLEX® BCN Assay Analytical Reactivity (Inclusivity) Summary by Organism

| Reportable Target (Family) | Reportable Target (Genus) | Reportable Target (Species) | Organism | Number of strains | Positivity |
| --- | --- | --- | --- | --- | --- |
| N/A | Acinetobacter spp. | N/A | Acinetobacter guillouiae | 1 | 100% |
| Acinetobacter radioresistens | 2 | 100% |
| Acinetobacter baylyi | 1 | 100% |
| Acinetobacter bereziniae | 1 | 100% |
| Acinetobacter calcoaceticus | 1 | 100% |
| Acinetobacter haemolyticus | 1 | 100% |
| Acinetobacter indicus | 1 | 100% |
| Acinetobacter johnsonii | 1 | 100% |
| Acinetobacter junii | 1 | 100% |
| Acinetobacter lwoffii | 1 | 100% |
| Acinetobacter nosocomialis | 1 | 100% |
| Acinetobacter pittii | 1 | 100% |
| Acinetobacter schindleri | 1 | 100% |
| Acinetobacter ursingii | 1 | 100% |
| Acinetobacter spp. | Acinetobacter baumannii | Acinetobacter baumannii | 5 | 100% |
| Enterobacteriaceae / Morganellaceae | Citrobacter spp. | N/A | Citrobacter amalonaticus | 2 | 100% |
| Citrobacter braakii | 2 | 100% |
| Citrobacter farmeri | 1 | 100% |
| Citrobacter freundii | 4 | 100% |
| Citrobacter gillenii | 1 | 100% |
| Citrobacter koseri | 5 | 100% |
| Citrobacter murliniae | 1 | 100% |
| Citrobacter rodentium | 1 | 100% |
| Citrobacter sedlakii | 1 | 100% |
| Citrobacter werkmanii | 1 | 100% |
| Citrobacter youngae | 1 | 100% |
| Enterobacteriaceae | Enterobacter | N/A | Enterobacter cloacae | 10 | 100% |

510(k) Summary

{22}

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LIAISON PLEX® Gram-Negative Blood Culture Assay Traditional 510(k)

| Reportable Target (Family) | Reportable Target (Genus) | Reportable Target (Species) | Organism | Number of strains | Positivity |
| --- | --- | --- | --- | --- | --- |
| / Morganellaceae | spp. | | Enterobacter aerogenes | 5 | 100% |
| | | | Enterobacter amnigenus | 1 | 100% |
| | | | Enterobacter asburiae | 1 | 100% |
| | | | Enterobacter bugandensis | 1 | 100% |
| | | | Enterobacter cancerogenus | 1 | 100% |
| | | | Enterobacter hormaechei | 2 | 100% |
| | | | Enterobacter ludwigii | 1 | 100% |
| Enterobacteriaceae / Morganellaceae | N/A | Escherichia coli | Escherichia coli | 21 | 100% |
| | | | Shigella boydii | 2 | 100% |
| | | | Shigella dysenteriae | 2 | 100% |
| | | | Shigella flexneri | 2 | 100% |
| | | | Shigella sonnei | 2 | 100% |
| Enterobacteriaceae / Morganellaceae | N/A | Klebsiella oxytoca | Klebsiella oxytoca | 5 | 100% |
| Enterobacteriaceae / Morganellaceae | N/A | Klebsiella pneumoniae | Klebsiella pneumoniae | 26 | 100% |
| Enterobacteriaceae / Morganellaceae | N/A | Klebsiella variicola | Klebsiella variicola | 5 | 100% |
| N/A | N/A | Haemophilus influenzae | Haemophilus influenzae | 6 | 100% |
| Enterobacteriaceae / Morganellaceae | N/A | Morganella morganii | Morganella morganii | 5 | 100% |
| N/A | N/A | Neisseria meningitidis | Neisseria meningitidis | 10 | 100% |
| Enterobacteriaceae / Morganellaceae | Proteus spp. | N/A | Proteus hauseri | 1 | 100% |
| | | | Proteus mirabilis | 5 | 100% |
| | | | Proteus myxofaciens | 1 | 100% |
| | | | Proteus penneri | 1 | 100% |
| | | | Proteus vulgaris | 2 | 100% |
| N/A | Pseudomonas spp. | N/A | Pseudomonas alcaligenes | 1 | 100% |
| | | | Pseudomonas chlororaphis | 1 | 100% |
| | | | Pseudomonas fluorescens | 1 | 100% |
| | | | Pseudomonas luteola | 1 | 100% |
| | | | Pseudomonas mendocina | 1 | 100% |
| | | | Pseudomonas monteilii | 1 | 100% |
| | | | Pseudomonas mosselii | 1 | 100% |
| | | | Pseudomonas | 1 | 100% |

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| Reportable Target (Family) | Reportable Target (Genus) | Reportable Target (Species) | Organism | Number of strains | Positivity |
| --- | --- | --- | --- | --- | --- |
| | | | mucidolens | | |
| | | | Pseudomonas oryzihabitans | 1 | 100% |
| | | | Pseudomonas pseudoalcaligenes | 1 | 100% |
| | | | Pseudomonas putida | 1 | 100% |
| | | | Pseudomonas resinovorans | 1 | 100% |
| | | | Pseudomonas stutzeri | 1 | 100% |
| | | | Pseudomonas veronii | 1 | 100% |
| | | Pseudomonas aeruginosa | Pseudomonas aeruginosa | 4 | 100% |
| Enterobacteriaceae / Morganellaceae | Salmonella spp. | N/A | Salmonella bongori | 1 | 100% |
| | | | Salmonella enterica | 12 | 100% |
| | | | Salmonella enterica subsp. arizonae | 1 | 100% |
| | | | Salmonella enterica subsp. diarizonae | 1 | 100% |
| | | | Salmonella enterica subsp. houtenae | 1 | 100% |
| | | | Salmonella enterica subsp. indica | 1 | 100% |
| N/A | N/A | Stenotrophomonas maltophilia | Stenotrophomonas maltophilia | 5 | 100% |
| Enterobacteriaceae / Morganellaceae | N/A | Serratia marcescens | Serratia marcescens | 6 | 100% |
| Enterobacteriaceae / Morganellaceae | N/A | N/A | Cedecea davisae | 2 | 100%^ |
| | | | Cedecea lapagei | 1 | 100%^ |
| | | | Cedecea neteri | 1 | 100% |
| | | | Cronobacter muytjensii | 1 | 100% |
| | | | Cronobacter sakazakii | 2 | 100% |
| | | | Enteric group 137 | 1 | 100% |
| | | | Escherichia albertii | 1 | 100%^ |
| | | | Escherichia fergusonii | 1 | 100% |
| | | | Escherichia hermanii | 1 | 100% |
| | | | Edwardsiella tarda | 1 | 100% |
| | | | Hafnia alvei | 1 | 100% |
| | | | Kluyvera ascorbata | 1 | 100%^ |
| | | | Kluyvera cryocrescens | 1 | 100% |
| | | | Kluyvera georgiana | 1 | 100% |
| | | | Kluyvera intermedia | 1 | 100% |
| | | | Leclercia adecarboxylata | 1 | 100%^ |

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| Reportable Target (Family) | Reportable Target (Genus) | Reportable Target (Species) | Organism | Number of strains | Positivity |
| --- | --- | --- | --- | --- | --- |
| | | | Lelliottia nimipressuralis | 1 | 100%^ |
| | | | Pantoea agglomerans | 1 | 100% |
| | | | Plesiomonas shigelloides | 1 | 100% |
| | | | Pluralibacter gergoviae | 1 | 100% |
| | | | Providencia acalifaciens | 1 | 100% |
| | | | Providencia heimbachae | 1 | 100% |
| | | | Providencia rettigeri | 1 | 100%^ |
| | | | Providencia stuartii | 1 | 100%^ |
| | | | Rahnella aquatillis | 1 | 100% |
| | | | Raoultella ornithinolytica | 1 | 100%^ |
| | | | Raoultella planticola | 1 | 100%^ |
| | | | Raoultella terrigena | 1 | 100%^ |
| | | | Serratia plymuthica | 1 | 100% |
| | | | Serratia grimesii | 1 | 100%^ |
| | | | Xenorhabdus bovienii | 1 | 100%^ |
| | | | Xenorhabdus poinarii | 1 | 100% |
| | | | Yersinia enterocolitica | 1 | 100% |
| | | | Yokenella regensburgei | 1 | 100% |
| | | | Serratia ficaria | 1 | 100%^ |
| | | | Serratia fonticola | 1 | 100%^ |
| | | | Serratia liquefaciens | 1 | 100%^ |
| | | | Serratia proteamaculans | 1 | 0%^ |
| | | | Serratia rubidaea | 1 | 100%^ |

^ { ^} See Table 8. Known Cross-Reactive Organisms

Table 7: LIAISON PLEX BCN Assay Analytical Reactivity (Inclusivity) Resistance Marker Summary

| Reportable Target (Resistance Marker) | Organism | # of strains | % Detected |
| --- | --- | --- | --- |
| CTX-M | Citrobacter freundii | 1 | 100% |
| | Enterobacter cloacae | 5 | 100% |
| | Escherichia coli | 14 | 100% |
| | Klebsiella oxytoca | 2 | 100% |
| | Klebsiella pneumoniae | 16 | 100% |
| | Kluyvera ascorbata | 1 | 100% |
| | Kluyvera georgiana | 1 | 100% |
| | Morganella morganii | 1 | 100% |
| | Salmonella enterica | 1 | 100% |
| IMP | Escherichia coli | 1 | 100% |
| | Klebsiella pneumoniae | 2 | 100% |
| | Proteus mirabilis | 1 | 100% |
| | Pseudomonas aeruginosa | 1 | 100% |

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LIAISON PLEX® Gram-Negative Blood Culture Assay Traditional 510(k)

| Reportable Target (Resistance Marker) | Organism | # of strains | % Detected |
| --- | --- | --- | --- |
| KPC | Citrobacter freundii | 2 | 100% |
| | Enterobacter cloacae | 1 | 100% |
| | Enterobacter hormaechei | 1 | 100% |
| | Klebsiella pneumoniae | 3 | 100% |
| | Morganella morganii | 1 | 100% |
| MCR | Enterobacter cloacae | 2 | 100% |
| | Escherichia coli | 5 | 100% |
| | Klebsiella pneumoniae | 4 | 100% |
| | Salmonella enterica | 2 | 100% |
| NDM | Enterobacter cloacae | 1 | 100% |
| | Escherichia coli | 4 | 100% |
| | Klebsiella pneumoniae | 1 | 100% |
| | Morganella morganii | 1 | 100% |
| OXA | Acinetobacter baumannii | 5 | 100% |
| | Acinetobacter radioresistens | 2 | 100% |
| | Acinetobacter indicus | 1 | 100% |
| | Escherichia coli | 2 | 100% |
| | Klebsiella pneumoniae | 5 | 100% |
| SME | Serratia marcescens | 6 | 100% |
| VIM | Enterobacter cloacae | 1 | 100% |
| | Klebsiella pneumoniae | 2 | 100% |
| | Pseudomonas aeruginosa | 3 | 100% |

Table 8: LIAISON PLEX® BCN Assay Known Analytical Reactivity (Inclusivity) Cross Reactive Organisms

| Cross-Reactive Organism | Strain ID | Expected Target | Additional Target DETECTED | Number Detected |
| --- | --- | --- | --- | --- |
| Cedecea davisae | ATCC 33431 | Enterobacteriaceae / Morganellaceae | Klebsiella oxytoca | 1/3 |
| Cedecea lapagei | ATCC 43028 | Enterobacteriaceae / Morganellaceae | Klebsiella oxytoca | 1/3 |
| Escherichia albertii | ATCC 46494 | Enterobacteriaceae / Morganellaceae | Escherichia coli | 2/3 |
| Kluyvera ascorbata | ATCC 33433 | Enterobacteriaceae / Morganellaceae | CTX-M | Klebsiella oxytoca | 3/3 |
| Leclercia adecarboxylata | ATCC 23216 | Enterobacteriaceae / Morganellaceae | Enterobacter spp. | 3/3 |
| Lelliottia nimipressuralis | ATCC 9912 | Enterobacteriaceae / Morganellaceae | Enterobacter spp. | 3/3 |
| Providencia rettigeri | ATCC 9250 | Enterobacteriaceae / Morganellaceae | Proteus spp. | 1/3 |
| Providencia stuartii | UTMB GN-403 | Enterobacteriaceae / Morganellaceae | Proteus spp. | 1/3 |

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LIAISON PLEX® Gram-Negative Blood Culture Assay Traditional 510(k)

| Cross-Reactive Organism | Strain ID | Expected Target | Additional Target DETECTED | Number Detected |
| --- | --- | --- | --- | --- |
| Raoultella ornithinolytica | ATCC 31898 | Enterobacteriaceae / Morganellaceae | Klebsiella oxytoca | 3/3 |
| Raoultella planticola | ATCC 33531 | Enterobacteriaceae / Morganellaceae | Klebsiella oxytoca | 3/3 |
| Raoultella terrigena | ATCC 33257 | Enterobacteriaceae / Morganellaceae | Citrobacter spp. | 3/3 |
| Serratia ficaria | ATCC 33105 | Enterobacteriaceae / Morganellaceae | Serratia marcescens | 3/3 |
| Serratia fonticola | ATCC 29844 | Enterobacteriaceae / Morganellaceae | Serratia marcescens | 3/3 |
| Serratia grimesii | ATCC 14461 | Enterobacteriaceae / Morganellaceae | Proteus spp. | 2/3 |
| Serratia liquefaciens | ATCC 27592 | Enterobacteriaceae / Morganellaceae | Serratia marcescens | 3/3 |
| Serratia proteamaculans | ATCC 35475 | Enterobacteriaceae / Morganellaceae# | Serratia marcescens | 3/3 |
| Serratia rubidaea | ATCC 27593 | Enterobacteriaceae / Morganellaceae | Serratia marcescens | 3/3 |
| Xenorhabdus bovienii | ATCC 35271 | Enterobacteriaceae / Morganellaceae | Proteus spp. | 2/3 |

# Expected Target not detected.

## Predicted (in silico) Reactivity (Inclusivity) Results

For all targets, in silico inclusivity analysis was performed using sequences available in the GenBank and WGS (whole genome shotgun) databases from February to April 2024. Alignments of the signal fragment for each target were generated using MAFFT (version 7.490). For all targets, the inclusivity analysis involved assessing the percent homology of each oligo sequence to its binding region on each target sequence retrieved from the public databases. The predicted inclusivity based on sequence homology is the percentage of sequences with at least 90% oligo identity. In determining oligo identity, the highest percent identity of each oligo in the same component was assessed and then the lowest percent identity of the two components (capture and mediator probes) is used to characterize the inclusivity of the sequence. In silico analysis results are summarized below in Table 9.

Table 9 – In silico Analysis Results

| Reportable Target | Inclusive Organism/Target | Total # Sequences in Alignment | # Sequences with Percent Oligo Identity ≥ 90% | Predicted Inclusivity Percentage (%) |
| --- | --- | --- | --- | --- |
| Acinetobacter baumannii | Acinetobacter baumannii | 1456 | 1450 | 100 |
| Acinetobacter spp. a | Acinetobacter spp. | 4451 | 4445 | 100 |
| Citrobacter spp. b | Citrobacter freundii | 440 | 440 | 100 |
| | Citrobacter koseri | 425 | 422 | 99 |
| | other Citrobacter species | 1065 | 1065 | 100 |

510(k) Summary

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LIAISON PLEX® Gram-Negative Blood Culture Assay Traditional 510(k)

| Reportable Target | Inclusive Organism/Target | Total # Sequences in Alignment | # Sequences with Percent Oligo Identity ≥ 90% | Predicted Inclusivity Percentage (%) |
| --- | --- | --- | --- | --- |
| Enterobacter spp.^{c} | Enterobacter cloacae | 266 | 266 | 100 |
| | Klebsiella / Enterobacter aerogenes | 1083 | 1083 | 100 |
| | other Enterobacter species | 3795 | 3777 | 100 |
| Enterobacteriaceae / Morganellaceae | Enterobacteriaceae | 28524 | 28442 | 100 |
| | Morganellaceae | 3829 | 3715 | 97 |
| Escherichia coli | Escherichia coli | 5083 | 5067 | 100 |
| | Shigella boydii | 711 | 711 | 100 |
| | Shigella dysenteriae | 277 | 277 | 100 |
| | Shigella flexneri | 246 | 246 | 100 |
| | Shigella sonnei | 1061 | 1061 | 100 |
| Haemophilus influenzae | Haemophilus influenzae | 236 | 236 | 100 |
| Klebsiella oxytoca^{d} | Klebsiella oxytoca species complex | 2117 | 2105 | 99 |
| Klebsiella pneumoniae | Klebsiella pneumoniae | 6163 | 6131 | 99 |
| Klebsiella variicola | Klebsiella variicola | 106 | 105 | 99 |
| Morganella morganii | Morganella morganii | 728 | 728 | 100 |
| Neisseria meningitidis | Neisseria meningitidis | 179 | 179 | 100 |
| Proteus spp.^{e} | Proteus spp. | 484 | 481 | 99 |
| Pseudomonas aeruginosa | Pseudomonas aeruginosa | 1341 | 1341 | 100 |
| Pseudomonas spp.^{f} | Pseudomonas spp. | 6480 | 6473 | 100 |
| Salmonella spp. | Salmonella bongori | 122 | 122 | 100 |
| | Salmonella enterica | 420 | 420 | 100 |
| | Salmonella enterica subsp. arizonae | 14 | 14 | 100 |
| | Salmonella enterica subsp. diarizonae | 21 | 21 | 100 |
| | Salmonella enterica subsp. enterica | 2164 | 2162 | 100 |
| | Salmonella enterica subsp. houtenae | 7 | 7 | 100 |
| | Salmonella enterica subsp. salamae | 26 | 26 | 100 |
| | Salmonella enterica subsp. VII | 2 | 2 | 100 |
| Serratia marcescens | Serratia marcescens | 262 | 262 | 100 |
| Stenotrophomonas maltophilia | Stenotrophomonas maltophilia | 410 | 408 | 100 |
| CTX-M^{g} | CTX-M | 12187 | 12146 | 100 |
| IMP^{h} | IMP | 1448 | 1441 | 100 |
| KPC^{i} | KPC | 4032 | 4031 | 100 |
| MCR^{j} | MCR-1 | 1695 | 1695 | 100 |
| | MCR-2 | 32 | 32 | 100 |
| | MCR-3 | 211 | 210 | 100 |
| NDM^{k} | NDM | 5426 | 5420 | 100 |
| OXA^{l} | OXA-23 family | 1721 | 1718 | 100 |
| | OXA-24/40/143 family | 403 | 403 | 100 |
| | OXA-48 family | 1968 | 1962 | 100 |
| | OXA-58 family | 425 | 425 | 100 |

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| Reportable Target | Inclusive Organism/Target | Total # Sequences in Alignment | # Sequences with Percent Oligo Identity ≥ 90% | Predicted Inclusivity Percentage (%) |
| --- | --- | --- | --- | --- |
| SME^{m} | SME | 189 | 188 | 99 |
| VIM^{n} | VIM | 1438 | 1438 | 100 |

a Includes sequences for 86 Acinetobacter species.
b Includes sequences for 17 Citrobacter species.
c Includes sequences for 22 Enterobacter species.
d Includes sequences for 6 members of the Klebsiella oxytoca species complex (KoSC).
e Includes sequences for 11 Proteus species.
f Includes sequences for 282 Pseudomonas species.
g Includes sequences for CTX-M-1 to CTX-M-269; not all types have sequences available.
h Includes sequences for IMP-1 to IMP-102; not all types have sequences available.
i Includes sequences for KPC-1 to KPC-208; not all types have sequences available.
j Includes sequences for MCR-1.1 to MCR1.37, MCR-2.1 and MCR-2.8, and MCR-3.1 to MCR-3.42; not all types have sequences available.
k Includes sequences for NDM-1 to NDM-61; not all types have sequences available.
l Includes sequences for OXA-23 family, OXA-24/40/143 family, OXA-48 family and OXA-58 family; not all types have sequences available.
m Includes sequences for SME-1 to SME-5; not all types have sequences available.
n Includes sequences for VIM-1 to VIM-86; not all types have sequences available.

## f. Analytical Specificity (Exclusivity)

### Cross-Reactivity

The analytical specificity study was performed to evaluate cross-reactivity of the LIAISON PLEX® BCN Assay through testing “off-panel” organisms, including both those phylogenetically related to the on-panel organisms and organisms likely to be present in typical blood culture samples. Out of the 113 off-panel species tested in triplicate, 17 species generated positive results. Summary results for all 113 species are listed in Table 10a. Of those 17 species that generated positive results, 11 species were cross-reactive and those cross-reactive calls are listed in Table 10b.

Table 10a: LIAISON PLEX® BCN Assay Analytical Specificity (Cross-Reactivity) Summary

| Organism | Positivity | Organism | Positivity |
| --- | --- | --- | --- |
| Gram Positive | | | |
| Abitrophia defectiva | 0% | Leuconostoc carnosum | 0% |
| Aerococcus viridans | 0% | Leuconostoc mesenteroides | 0% |
| Arcanobacterium bernardiae | 0% | Listeria grayi | 0% |
| Arcanobacterium haemolyticum | 0% | Listeria innocua | 0% |
| Bacillus cereus | 0% | Listeria ivanovii | 0% |
| Bacillus licheniformins | 0% | Listeria welshimeri | 0% |
| Bacillus subtilis | 0% | Micrococcus luteus | 0% |
| Bacillus thuringiensis | 0% | Micrococcus lylae | 0% |
| Corynebacterium amycolatum | 0% | Pediococcus acidilactici | 0% |
| Corynebacterium diphtheriae | 0% | Pediococcus pentosaceus | 0% |

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| Organism | Positivity | Organism | Positivity |
| --- | --- | --- | --- |
| Corynebacterium pseudodiptheriticum | 0% | Peptostreptococcus anaerobius | 0% |
| Corynebacterium striatum | 0% | Planococcus citreus | 0% |
| Cutibacterium acnes | 0% | Planococcus kocurii | 0% |
| Cutibacterium avidum | 0% | Rothia dentocariosa | 0% |
| Propionibacterium freudenreichii | 0% | Rothia (Stomatococcus) mucilaginosa | 0% |
| Enterococcus avium | 0% | Staphylococcus capitis | 0% |
| Enterococcus casseliflavis, VRE, vanC | 0% | Staphylococcus caprae | 0% |
| Enterocococcus dispar | 0% | Staphylococcus cohnii | 0% |
| Enterococcus durans | 0% | Staphylococcus haemolyticus | 0% |
| Enterococcus flavescens | 0% | Staphylococcus hominis | 0% |
| Enterococcus gallinarum, vanC | 0% | Staphylococcus intermedius | 0% |
| Enterococcus hirae | 0% | Staphylococcus lugdunensis | 0% |
| Enterococcus mundtii | 0% | Streptococcus agalactiae | 0% |
| Enterococcus raffinosus | 0% | Streptococcus anginosus | 0% |
| Erysipelothrix rhusiopathiae | 0% | Streptococcus bovis | 0% |
| Kocuria kristinae | 0% | Streptococcus constellatus | 0% |
| Kytococcus sedentarius, Met R | 0% | Streptococcus equinus | 0% |
| Lactobacillus acidophilus | 0% | Streptococcus mitis | 0% |
| Lactobacillus crispatus | 0% | Streptococcus pneumoniae | 0% |
| Lactobacillus rhamnosus | 0% | Streptococcus pyogenes | 0% |
| Corynebacterium frankenforstense | 0% | | |
| Gram Negative | | | |
| Aggregatibacter aphrophilus | 0% | Fusobacterium nucleatum | 0% |
| Bacteroides fragilis | 0% | Haemophilus haemolyticus | 0% |
| Brevundimonas diminuta | 0% | Herbaspirillum huttiense | 0% |
| Burkholderia cepacia | 0% | Kingella kingae | 0% |
| Capnocytophaga ochracea | 0% | Moraxella catarrhalis | 0% |
| Cardiobacterium hominis | 0% | Neisseria lactamica | 0% |
| Comamonas testosteroni | 0% | Neisseria mucosa | 0% |
| Delftia acidovorans | 0% | Neisseria sicca | 0% |
| Eikenella corrodens | 0% | Parabacteroides distasonis | 0% |
| Elizabethkingia meningoseptica | 0% | Pasteurella aerogenes | 0% |
| Fusobacterium necrophorum | 0% | Prevotella bivia | 0% |
| Aeromonas hydrophila | 0% | Klebsiella quasivariicola | 100% |
| Haemophilus parainfluenzae | 0% | Providencia rustigiani | 100% |
| Haemophilus parahaemolyticus | 33% | Providencia vermicola | 100% |
| Enterobacter kobei | 100% | Pseudomonas paraeruginosa | 100% |
| Haemophilus aegyptius | 100% | Serratia entomophila | 100% |
| Klebsiella grimontii | 100% | Serratia nevei | 100% |
| Klebsiella huaxiensis | 100% | Serratia odorifera | 100% |
| Klebsiella michiganensis | 100% | Serratia quinivorans | 100% |
| Klebsiella quasipneumoniae | 100% | Serratia ureilytica | 100% |
| Lelliottia amnigena | 100% | | |

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| Organism | Positivity | Organism | Positivity |
| --- | --- | --- | --- |
| Yeast/Fungi | | | |
| Aspergillus fumigatus | 0% | Candida tropicalis | 0% |
| Candida albicans | 0% | Cryptococcus neoformans | 0% |
| Candida famata | 0% | Kluyveromyces lactis | 0% |
| Candida glabrata | 0% | Saccharomyces cerevisiae | 0% |
| Candida krusei | 0% | Schizosaccharomyces pombe | 0% |
| Candida parapsilosis | 0% | | |

Table 10b: LIAISON PLEX® BCN Assay Cross-Reactive Organisms Summary

| Organism | Positivity | Results | |
| --- | --- | --- | --- |
| Not Reported to Cause Bloodstream Infections | | | |
| | | Inclusive | Cross-reacting |
| Lelliottia amnigena | 100% | Enterobacteriaceae / Morganellaceae | Enterobacter spp. |
| Pseudomonas paraeruginosa | 100% | Pseudomonas spp. | Pseudomonas aeruginosa |
| Serratia nevei | 100% | Enterobacteriaceae / Morganellaceae | Serratia marcescens |
| Serratia entomophila | 100% | Enterobacteriaceae / Morganellaceae | Serratia marcescens |
| Serratia ureilytica | 100% | Enterobacteriaceae / Morganellaceae | Serratia marcescens |
| Klebsiella quasivariicola | 100% | Enterobacteriaceae / Morganellaceae | Klebsiella pneumoniae |
| Rare/Not Primarily Associated with Bloodstream Infections | | | |
| | | Inclusive | Cross-reacting |
| Haemophilus aegyptius | 100% | None | Haemophilus influenzae |
| Klebsiella michiganensis | 100% | Enterobacteriaceae / Morganellaceae | Klebsiella oxytoca |
| Rare/Opportunistic with Some Documented Bloodstream Infection Cases | | | |
| | | Inclusive | Cross-reacting |
| Klebsiella grimontii | 100% | Enterobacteriaceae / Morganellaceae | Klebsiella oxytoca |
| Klebsiella quasipneumoniae | 100% | Enterobacteriaceae / Morganellaceae | Klebsiella pneumoniae |
| Haemophilus parahaemolyticus | 33% | None | Enterobacteriaceae / Morganellaceae |

## In Silico Cross-Reactivity

In silico exclusivity assessment of the oligo sequences incorporated in the assay designs was performed against on-panel and off-panel organisms listed in Table 11. Based on the analysis of sequences available in the GenBank nucleotide database as of June 7, 2024, the following potential cross-reactivity is predicted:

- Acinetobacter baumannii oligo designs are predicted to detect some strains of Acinetobacter pittii and Klebsiella pneumoniae.
- Some strains of Escherichia species (E. albertii, E. coli, E. fergusonii, E. marmotae), Raoultella terrigena and Shigella species (S. boydii, S. dysenteriae, S. flexneri, S. sonnei) are predicted to produce false positive Citrobacter spp. results.
- Enterobacter spp. oligo designs are predicted to detect some strains of Klebsiella huaxiensis, Leclercia adecarboxylata and Lelliottia species (Lelliottia amnigena, Lelliottia nimipressuralis).
- Some strains of Aeromonas hydrophila, Aggregatibacter aphrophilus, Corynebacterium frankenforstense, Haemophilus parahaemolyticus, Haemophilus parainfluenzae and

510(k) Summary

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Pseudomonas wenzhouensis are predicted to produce false positive Enterobacteriaceae / Morganellaceae results.

- Escherichia coli oligo designs are predicted to detect some strains of Escherichia albertii and Escherichia marmotae.
- Haemophilus influenzae oligo designs are predicted to detect some strains of Haemophilus aegyptius.
- Some strains of Cedecea species (C. davisae, C. lapagei, C. neteri), Enterobacter species (E. kobei, E. mori), Escherichia coli, Klebsiella species (K. aerogenes, K. electrica, K. grimontii, K. huaxiensis, K. michiganensis, K. pasteurii, K. pneumoniae, K. variicola), Kluyvera species (K. ascorbate, K. cryocrescens), Raoultella species (R. ornithinolytica, R. planticola) and unspecified Superficieibacter species are predicted to produce false positive Klebsiella oxytoca results.
- Klebsiella pneumoniae oligo designs are predicted to detect some strains of Enterobacteriaceae bacterium and Klebsiella species (K. africana, K. grimontii, K. quasipneumoniae, K. quasivariicola, K. variicola).
- Some strains of Cronobacter muytjensii, Klebsiella pneumoniae and Klebsiella quasipneumoniae are predicted to produce false positive Klebsiella variicola results.
- Some strains of Arsenophonus species (A. apicola, A. endosymbiont, A. nasoniae), Haemophilus parahaemolyticus, Leclercia adecarboxylata, Morganella psychrotolerans, Providencia species (P. hangzhouensis, P. heimbachae, P. huaxiensis, P. manganoxydans, P. rettgeri, P. rustigianii, P. stuartii, P. vermicola), Serratia species (S. grimesii, S. proteamaculans, S. quinivorans) and Xenorhabdus species (X. bovienii, X. budapestensis, X. griffiniae, X. hominickii, X. poinarii) are predicted to produce false positive Proteus spp. results.
- Pseudomonas aeruginosa oligo designs are predicted to detect some strains of Pseudomonas paraeruginosa and Pseudomonas fluorescens.
- Salmonella spp. oligo designs are predicted to detect one strain of Enterobacteriaceae bacterium.
- Some strains of Serratia species (S. bockelmannii, S. entomophila, S. ficaria, S. fonticola, S. grimesii, S. inhibens, S. liquefaciens, S. nematodiphila, S. nevei, S. odorifera, S. proteamaculans, S. quinivorans, S. rhizosphaerae, S. rubidaea, S. surfactantfaciens, S. symbiotica, S. ureilytica) are predicted to produce false positive Serratia marcescens results.
- Stenotrophomonas maltophilia oligo designs are predicted to detect some strains of Enterobacter cloacae and other Stenotrophomonas species (S. acidaminiphila, S. nitritireducens, S. rhizophila).
- Some strains of Serratia liquefaciens are predicted to produce false positive Serratia marcescens and CTX-M results.
- Some strains of Serratia liquefaciens and Serratia nevei are predicted to produce false positive Serratia marcescens and IMP results.
- Some strains of Serratia nevei are predicted to produce false positive Serratia marcescens and OXA results.

Table 11. Potential Cross-Reactive Organisms assessed in the In Silico Exclusivity Analysis

| On-Panel Organisms | Off-Panel Organisms | | | |
| --- | --- | --- | --- | --- |
| | Gram-Positive Bacteria | Gram-Negative Bacteria | Resistance Markers | Yeasts / Viruses / Parasites |
| Acinetobacter baumannii | Actinomyces israelii | Actinobacillus hominis | AmpC | Aspergillus flavus |
| Acinetobacter spp. | Actinomyces naeslundii | Actinobacillus ureae | CMY | Aspergillus fumigatus |
| Citrobacter spp. | Actinomyces odontolyticus | Aeromonas caviae | mecA | Aspergillus niger |
| Enterobacter spp. | Aerococcus sanguinicola | Aeromonas hydrophila | mecC | Aspergillus terreus |

510(k) Summary

{32}

Diasorin

LIAISON PLEX® Gram-Negative Blood Culture Assay Traditional 510(k)

| On-Panel Organisms | Off-Panel Organisms | | | |
| --- | --- | --- | --- | --- |
| | Gram-Positive Bacteria | Gram-Negative Bacteria | Resistance Markers | Yeasts / Viruses / Parasites |
| Enterobacteriaceae | Aerococcus urinae | Aeromonas sobria | ompK36 | Blastomyces dermatitidis |
| Escherichia coli / Shigella spp. | Aerococcus viridans | Aggregatibacter actinomycetemcomitans | RAHN | Candida albicans |
| Haemophilus influenzae | Arcanobacterium bernardiae | Aggregatibacter aphrophilus | SHV | Candida auris |
| Klebsiella oxytoca | Arcanobacterium haemolyticum | Bacteroides caccae | SPM | Candida dubliniensis |
| Klebsiella pneumoniae | Arthrobacter…