The LIAISON PLEX Yeast Blood Culture (BCY) Assay is a qualitative nucleic acid multiplex in vitro diagnostic test intended for use on the LIAISON PLEX System for simultaneous detection and identification of multiple potentially pathogenic fungal organisms in positive blood culture. The LIAISON PLEX BCY Assay is performed directly on blood culture samples identified as positive by a continuous monitoring blood culture system and which contain fungal organisms as determined by Gram Stain. The LIAISON PLEX BCY Assay detects and identifies the following fungal organisms:

Candida albicans
Candida auris
Candida dubliniensis
Candida famata
Candida glabrata
Candida guilliermondii
Candida kefyr
Candida krusei
Candida lipolytica
Candida lusitaniae
Candida parapsilosis
Candida tropicalis
Candida haemulonii / duobushaemulonii
Cryptococcus neoformans / gattii

The detection and identification of specific fungal nucleic acids from individuals exhibiting signs and/or symptoms of bloodstream infection aids in the diagnosis of bloodstream infection when used in conjunction with other clinical information. The results from LIAISON PLEX BCY Assay are intended to be interpreted in conjunction with Gram stain results and should not be used as the sole basis for diagnosis, treatment management decisions.

Negative results in the setting of a suspected bloodstream infection with pathogens that are not detected by this test. Positive results do not rule out co-infection with other organisms; the organism(s) detected by LIAISON PLEX BCY Assay may not be the definite cause of disease. Additional laboratory testing (e.g. sub-culturing of positive blood cultures for identification of organisms not detected by LIAISON PLEX BCY Assay, susceptibility testing and differentiation of mixed growth) and clinical presentation must be taken into consideration in the final diagnosis of bloodstream infection.

Device Description

The LIAISON PLEX "Yeast Blood Culture Assay (BCY 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 a fungal organism, as determined by a Gram stain. The system consists of an instrument, a single-use disposable test cartridge, and a transfer pipette. The user loads the sample into the sample port of the LIAISON PLEX Yeast 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 BCY 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) Amplification: Multiplex PCR based amplification of the extracted nucleic acid to generate target specific amplicons; c) Hybridization: Amplified DNA hybridizes to specific capture DNA arrayed on a glass slide in a microarray format and the bound target DNA, in turn, hybridizes with mediator and gold-nanoparticle probes; d) 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.

AI/ML Overview

Acceptance Criteria and Device Performance for LIAISON PLEX Yeast Blood Culture Assay

The LIAISON PLEX Yeast Blood Culture (BCY) Assay is a qualitative nucleic acid multiplex in vitro diagnostic test for the simultaneous detection and identification of multiple potentially pathogenic fungal organisms in positive blood cultures. The study summarized below aimed to demonstrate the device meets its acceptance criteria through analytical and clinical performance evaluations.

1. Table of Acceptance Criteria and Reported Device Performance

The acceptance criteria for the LIAISON PLEX BCY Assay clinical study were predefined as:

Sensitivity: ≥ 90% for all targets
Specificity: ≥ 95% for each target
Failure rate: ≤ 15%

The clinical performance data, combining prospective and pre-selected specimens, is summarized in the table below, comparing it against the acceptance criteria.

Table 1: LIAISON PLEX BCY Assay Clinical Performance (Acceptance Criteria vs. Reported Performance)

Pathogen Target	Acceptance Criteria (Sensitivity)	Reported Sensitivity/PPA (Combined)	Acceptance Criteria (Specificity)	Reported Specificity/NPA (Combined)	Overall Failure Rate (Initial Run)	Overall Failure Rate (After Retest)	Acceptance Criteria (Failure Rate)
Candida albicans	≥ 90%	100.0% (34/34)	≥ 95%	99.0% (97/98)	2.9% (Overall)	0.2% (Overall)	≤ 15%
Candida auris	≥ 90%	100.0% (4/4)	≥ 95%	100.0% (128/128)
Candida dubliniensis	≥ 90%	NA (0/0)	≥ 95%	100.0% (132/132)
Candida famata	≥ 90%	NA (0/0)	≥ 95%	100.0% (132/132)
Candida glabrata	≥ 90%	100.0% (46/46)	≥ 95%	100.0% (86/86)
Candida guilliermondii	≥ 90%	NA (0/0)	≥ 95%	100.0% (132/132)
Candida haemulonii/C. duobushaemulonii	≥ 90%	NA (0/0)	≥ 95%	100.0% (132/132)
Candida kefyr	≥ 90%	100.0% (1/1)	≥ 95%	100.0% (131/131)
Candida krusei	≥ 90%	100.0% (4/4)	≥ 95%	100.0% (128/128)
Candida lipolytica	≥ 90%	NA (0/0)	≥ 95%	100.0% (132/132)
Candida lusitaniae	≥ 90%	100.0% (2/2)	≥ 95%	100.0% (130/130)
Candida parapsilosis	≥ 90%	100.0% (17/17)	≥ 95%	99.1% (114/115)
Candida tropicalis	≥ 90%	100.0% (6/6)	≥ 95%	97.6% (123/126)
Cryptococcus neoformans/Cryptococcus gattii	≥ 90%	100.0% (5/5)	≥ 95%	100.0% (127/127)

NA = Not applicable, as there were no positive cases for this target in the combined prospective/pre-selected dataset to calculate sensitivity, or no negative cases to calculate specificity.

The reported performance demonstrates that the LIAISON PLEX BCY Assay met all defined acceptance criteria.

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

The test set for the clinical performance evaluation utilized a combination of prospective, pre-selected, and contrived specimens:

Prospective Specimens (Clinical Study): 69 unique specimens from four geographically diverse clinical sites in the United States. These were collected prospectively between June 2023 and October 2023. One initial specimen was excluded due to an inconclusive Gram stain result.
Pre-selected Specimens (Clinical Study): 63 remnant, de-identified specimens sourced from 6 different sites/vendors in the United States. The data provenance is retrospective clinical specimens that were pre-characterized.
Contrived Specimens: 829 specimens were artificially generated. These were blinded, randomized, and tested at all four testing sites during June 2023. These are contrived data.

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

The provided document does not explicitly state the number of experts or their specific qualifications (e.g., radiologist with 10 years of experience) used to establish the ground truth for the test set.

However, the ground truth for the clinical study was established by comparing the LIAISON PLEX BCY Assay's performance against a Standard of Care culture followed by identification by Matrix Assisted Laser Desorption/Ionization coupled to time-of-flight Mass Spectrometry (MALDI-TOF MS) for all fungal targets. For the pre-selected specimens, it is mentioned that they were "characterized by an FDA cleared molecular assay prior to enrollment in the study." This implies that the ground truth relied on established laboratory methodologies and potentially an FDA-cleared reference method.

4. Adjudication Method for the Test Set

The document does not describe an adjudication method like "2+1" or "3+1" using human experts for the clinical study. The comparison was made against a "Standard of Care culture followed by identification by MALDI-TOF MS" as the reference method, which serves as the definitive ground truth for the presence and identification of the fungal organisms. For the pre-selected specimens, an "FDA cleared molecular assay" was used for characterization prior to study entry. These are objective laboratory methods rather than subjective expert interpretations requiring adjudication.

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 reported. This device is an in vitro diagnostic (IVD) assay designed for automated detection and identification of fungal organisms directly from blood culture samples. Its performance is evaluated against laboratory reference methods (culture and MALDI-TOF MS, or existing molecular assays), not against human reader interpretation of images or other subjective assessments. Therefore, there is no discussion of how human readers improve with or without AI assistance, as AI assistance is not part of the described use case for this IVD device.

6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) was done

Yes, the performance presented for the LIAISON PLEX BCY Assay in the analytical and clinical performance sections is for the standalone algorithm/device performance directly on the sample, without human interpretation or intervention in the diagnostic output. The system automates sample analysis, including nucleic acid extraction, amplification, hybridization, and signal analysis, to generate detected or not detected results. The indication for use clearly states the results are "intended to be interpreted in conjunction with Gram stain results and should not be used as the sole basis for diagnosis, treatment management decisions," but this refers to the clinical application context, not a human-in-the-loop for the device's fundamental diagnostic accuracy calculation.

7. The Type of Ground Truth Used

The primary ground truth used for the clinical study was:

Standard of Care culture followed by identification by Matrix Assisted Laser Desorption/Ionization coupled to time-of-flight Mass Spectrometry (MALDI-TOF MS). This is a laboratory-based, objective method for identifying microorganisms.
For pre-selected specimens, ground truth was established by an previously FDA-cleared molecular assay.
For contrived specimens, the ground truth was inherently known based on how the samples were prepared (spiking known organisms).

8. The Sample Size for the Training Set

The document does not report specific sample sizes for a separate training set for this device. The information provided heavily details analytical and clinical verification/validation (test set) studies. For diagnostic devices like this (nucleic acid assays), the development process typically involves extensive analytical characterization (Limit of Detection, Inclusivity, Exclusivity, Interference, Reproducibility) and then clinical validation. It is probable that internal development, optimization, and early verification studies used various sets of samples, but these are not explicitly termed "training sets" in the context of machine learning model training as one might expect for AI/ML-based diagnostic software.

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

As no explicit "training set" is documented (in the context of AI/ML), there is no description of how ground truth was established for such a set. However, for the analytical studies and development of the assay, ground truth would have been established through well-characterized reference strains and clinical isolates, quantified using standard microbiology techniques (e.g., CFU/mL for Limit of Detection). These methods involve culturing, molecular characterization, and established laboratory practices to confirm the identity and concentration of the microorganisms.

Summary

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June 4, 2024

Image /page/0/Picture/1 description: The image contains the logo of the U.S. Food and Drug Administration (FDA). On the left is the Department of Health & Human Services logo. To the right of that is the FDA logo, which is a blue square with the letters "FDA" in white. To the right of the FDA logo is the text "U.S. FOOD & DRUG ADMINISTRATION" in blue.

Luminex Corporation Sarah Herzog Sr. Regulatory Affairs Associate 4088 Commercial Avenue Northbrook, Illinois 60062

Re: K240627

Trade/Device Name: LIAISON PLEX Yeast 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: PEO, NSU Dated: March 5, 2024 Received: March 6, 2024

Dear Sarah Herzog:

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.

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).

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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 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 mediation-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).

Sincerelv.

Noel J. Gerald -S

Noel J. Gerald, Ph.D. Branch Chief Bacterial Respiratory and Medical Countermeasures Branch Division of Microbiology Devices OHT7: Office of In Vitro Diagnostics Office of Product Evaluation and Quality Center for Devices and Radiological Health

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Indications for Use

510(k) Number (if known) K240627

Device Name LIAISON PLEX Yeast Blood Culture Assay

Indications for Use (Describe)

Candida albicans Candida auris Candida dubliniensis Candida famata Candida glabrata Candida guilliermondii Candida kefyr Candida krusei Candida lipolytica Candida lusitaniae Candida parapsilosis Candida tropicalis Candida haemulonii / duobushaemulonii Cryptococcus neoformans / gattii

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

X Prescription Use (Part 21 CFR 801 Subpart D)

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

CONTINUE ON A SEPARATE PAGE IF NEEDED.

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Image /page/4/Picture/0 description: The image shows the logo for Luminex. The word "Luminex" is written in a bold, black font, with a red dot above the "i". Below the logo is the tagline "complexity simplified.", with a red dot at the end.

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: 05 March 2024

A. 510(k) Number:

K240627

B. Purpose for Submission:

Traditional 510(k), New Device

C. Measurand:

Candida albicans, Candida auris, Candida dublinensis, Candida qlabrata, Candida guilliermondii, Candida kefyr, Candida krusei, Candida lipolytica, Candida lusitaniae, Candida parapsilosis, Candida tropicalis, Candida haemulonii/duobushaemulonii, and Cryptococcus neoformans/gatti

D. Type of Test:

Qualitative Real Time Polymerase Chain Reaction (PCR)

E. Applicant:

Sarah Herzog, Luminex Corporation 4088 Commercial Avenue Northbrook, IL 60062 (847) 400-9000

F. Proprietary and Established Names:

LIAISON PLEX® Yeast Blood Culture Assay

G. Regulatory Information:

ProductCode	Classification	Regulation Section	Panel
PEO	II	21 CFR 866.3365 – Multiplex Nucleic AcidAssay for Identification of Microorganismsand Resistance Markers from PositiveBlood Cultures	83 (Microbiology)

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complexity simplit

LIAISON PLEX® Yeast Blood Culture Assay Traditional 510(k) Submission

H. Intended Use:

1. Intended use(s):

The LIAISON PLEX® Yeast Blood Culture (BCY) Assay is a qualitative nucleic acid multiplex in vitro diagnostic test intended for use on the LIAISON PLEX® System for simultaneous detection and identification of multiple potentially pathogenic fungal organisms in positive blood culture. The LIAISON PLEX® BCY Assay is performed directly on blood culture samples identified as positive by a continuous monitoring blood culture system and which contain fungal organisms as determined by Gram Stain.

The LIAISON PLEX® BCY Assay detects and identifies the following fungal organisms:

Candida albicans
Candida auris
Candida dubliniensis
Candida famata
Candida glabrata
Candida guilliermondii
Candida kefyr
Candida krusei
Candida lipolytica
Candida lusitaniae
Candida parapsilosis
Candida tropicalis
Candida haemulonii/duobushaemulonii
Cryptococcus neoformans/gattii

The detection and identification of specific fungal nucleic acids from individuals exhibiting signs and/or symptoms of bloodstream infection aids in the diagnosis of bloodstream infection when used in conjunction with other clinical information. The results from LIAISON PLEX® BCY Assay are intended to be interpreted in conjunction with Gram stain results and should not be used as the sole basis for diagnosis, treatment, or other patient management decisions.

Negative results in the setting of a suspected bloodstream infection may be due to infection with pathogens that are not detected by this test. Positive results do not rule out co-infection with other organisms; the organism(s) detected by LIAISON PLEX® BCY Assay may not be the definite cause of disease. Additional laboratory testing (e.g. sub-culturing of positive blood cultures for identification of organisms not detected by LIAISON PLEX® BCY Assay, susceptibility testing and differentiation of mixed growth) and clinical presentation must be taken into consideration in the final diagnosis of bloodstream infection.

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

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LIAISON PLEX® Yeast Blood Culture Assay Traditional 510(k) Submission 3. Special conditions for use statement(s):
For prescription use only.

For in vitro diagnostic use only.

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

l. Device Description:

Substantial Equivalence Information: J.

1. Predicate device name(s): GenMark ePlex Blood Culture Identification Fungal Pathogen (BCID-FP)
1. Predicate 510(k) number(s): K182690
1. Comparison with predicate:

The following tables compare Luminex's LIAISON® Yeast Blood Culture Assay to the ePlex Blood Culture Identification Fungal Pathogen (BCID-FP).

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LIAISON PLEX® Yeast Blood Culture Assay Traditional 510(k) Submission

Comparison to Predicate

	Predicate Device:	Candidate Device:
Comparisonto PredicateDevice	GenMark ePlex Blood Culture IdentificationFungal Pathogen (BCID-FP), K182690	LIAISON PLEX® Yeast Blood Culture Assay
Product Code	PEO	PEO
Regulation Number	21 CFR 866.3365	21 CFR 866.3365
Organism Detected	Candida albicans, Candida auris, Candidadubliniensis, Candida famata, Candidaglabrata, Candida guilliermondii, Candidakefyr, Candida krusei, Candida lusitaniae,Candida parapsilosis, Candida tropicalis,Cryptococcus gattii, Cryptococcusneoformans, Fusarium, Rhodotorula	Candida albicans, Candida auris, Candidadublinensis,Candida famata, Candida glabrata,Candida guilliermondii, Candida kefyr,Candida krusei, Candida lipolytica,Candida lusitaniae, Candida parapsilosis,Candida tropicalis, Candida haemulonii/duobushaemulonii, Cryptococcusneoformans/gatti
Measurand	Nucleic acid from Organisms detected	Nucleic acid from Organisms detected
Intended Use	The GenMark ePlex Blood CultureIdentification Fungal Pathogen (BCID-FP)Panel is a qualitative nucleic acid multiplexin vitro diagnostic test intended for use onGenMark's ePlex Instrument forsimultaneous detection and identification ofmultiple potentially pathogenic fungalorganisms in positive blood culture. TheePlex BCID-FP Panel is performed directly onblood culture samples identified as positiveby a continuous monitoring blood culturesystem and which contains fungalorganisms.The following fungal organisms are identifiedusing the ePlex BCID-FP Panel:	The LIAISON PLEX Yeast Blood Culture(BCY) Assay is a qualitative nucleic acidmultiplex in vitro diagnostic test intendedfor use on the LIAISON PLEX System forsimultaneous detection and identificationof multiple potentially pathogenic fungalorganisms in positive blood culture. TheLIAISON PLEX BCY Assay is performeddirectly on blood culture samplesidentified as positive by a continuousmonitoring blood culture system andwhich contain fungal organisms asdetermined by Gram Stain.The LIAISON PLEX BCY Assay detects andidentifies the following fungal organisms:
	Candida albicans Candida auris Candida dubliniensis Candida famata Candida glabrata Candida guilliermondii Candida kefyr Candida krusei Candida lusitaniae Candida parapsilosis Candida tropicalis Cryptococcus gattii Cryptococcus neoformans Fusarium Rhodotorula	Candida albicans Candida auris Candida dublinensis Candida famata Candida glabrata Candida guilliermondii Candida kefyr Candida krusei Candida lipolytica Candida lusitaniae Candida parapsilosis Candida tropicalis Candida haemulonii/duobushaemulonii Cryptococcus neoformans/gatti
	The detection and identification of specificfungal nucleic acids from individualsexhibiting signs and/or symptoms ofbloodstream infection aids in the diagnosisof bloodstream infection when used inconjunction with other clinical information.The results from the ePlex BCID-FP Panelare intended to be interpreted inconjunction with Gram stain results andshould not be used as the sole basis fordiagnosis, treatment, or other patientmanagement decisions.Negative results in the setting of asuspected bloodstream infection may bedue to infection with pathogens that are notdetected by this test. Positive results do notrule out co-infection with other organisms;the organism(s) detected by the ePlex BCID-FP Panel may not be the definite cause ofdisease. Additional laboratory testing (e.g.sub-culturing of positive blood cultures foridentification of organisms not detected byePlex BCID-FP Panel, susceptibility testingand differentiation of mixed growth) andclinical presentation must be taken intoconsideration in the final diagnosis ofbloodstream infection.	The detection and identification ofspecific fungal nucleic acids fromindividuals exhibiting signs and/orsymptoms of bloodstream infection aidsin the diagnostic of bloodstreaminfection when used in conjunction withother clinical information. The resultsfrom the LIAISON PLEX BCY Assay areintended to be interpreted inconjunction with Gram stain results andshould not be used as the sole basis fordiagnosis, treatment, or other patientmanagement decisions.Negative results in the setting of asuspected bloodstream infection may bedue to infection with pathogens that arenot detected by this test. Positive resultsdo not rule out co-infection with otherorganisms; the organism(s) detected byLIAISON PLEX BCY Assay may not be thedefinite cause of disease. Additionallaboratory testing (e.g. sub-culturing ofpositive blood cultures for identificationof organisms not detected by LIAISONPLEX BCY Assay, susceptibility testingand differentiation of mixed growth) andclinical presentation must be taken intoconsideration in the final diagnosis ofbloodstream infection.
Automated System(Sample to Answer)	Automated	Same
Instrumentation	ePlex Instrument	LIAISON PLEX®
Sample Types	Blood Culture	Same

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LIAISON PLEX® Yeast Blood Culture Assay Traditional 510(k) Submission

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LIAISON PLEX® Yeast Blood Culture Assay Traditional 510(k) Submission

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 27, 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.
. CLSI. Interference Testing in Clinical Chemistry. 3rd ed. CLSI guideline EP07. Wayne, PA: Clinical and Laboratory Standards Institute; 2018.
ISO 14971:2019 Medical devices - Application of risk management to medical devices
. IEC 62366-1:2015 Medical devices - Part 1: Application of usability engineering to medical devices
. ISO 62304:2006 Medical device software - Software life-cycle processes
. ISO 15223-1:2016: Medical Devices - Symbols to be used with medical device labels, labeling and information to be supplied - Part 1: General requirements
. IEC 61010-1 Ed. 3.0 2010: 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

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LIAISON PLEX® Yeast Blood Culture Assay Traditional 510(k) Submission

. 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
. 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® Yeast Blood Culture Assay (BCY 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 a fungal organism, as determined by a Gram stain. The system consists of an instrument and a single-use, disposable test cartridge and a transfer pipette. The user loads the sample into the sample port of the LIAISON PLEX® Yeast 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® BCY 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) Amplification: Multiplex PCR based amplification of the extracted nucleic acid to generate target specific amplicons; c) Hybridization: Amplified DNA hybridizes to specific capture DNA arrayed on a glass slide in a microarray format and the bound target DNA, in turn, hybridizes with mediator and goldnanoparticle probes; d) 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.

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M. Performance Characteristics:

1. Analytical performance:

a. Analytical Sensitivity (Limit of Detection)

A limit of detection study (LoD) was performed to evaluate the analytical sensitivity of the LIAISON Plex® BCY Assay. Twenty-eight (28) strains and isolates that represent the 14 reportable targets of the LIAISON Plex BCY Assay were tested individually by serially diluting each target in a simulated blood culture sample matrix. Testing was broken into two parts; Preliminary LoD and Confirmation LoD. The Preliminary LoD concentrations were evaluated using a 6 point 3-fold dilution series and testing of at least four replicates per dilution. The Preliminary LoD for each target was defined as the lowest concentration at which 100% of four replicates were positive for the intended reportable target. With the preliminary LoD results, a 3-point 3 fold dilution series was made. Twenty replicates of each applicable dilution series were tested. Two concentrations were required with 20 replicates each to help determine the confirmed LoD for each strain. The confirmed LoD for each organism was defined as the lower concentration at which ≥ 95% of the 20 replicates were positive for the intended reportable target. The confirmed LoD for each target tested is listed in the following Table 1.

LIAISON PLEX Target	Organism	Source & ID	ConfirmedLoD (CFU/mL)
Candida albicans	Candida albicans	ATCC 10231	3.14E+04
Candida albicans	Candida albicans	ATCC 14053	2.83E+05
Candida kefyr	Candida kefyr	ATCC 8553	3.33E+03
Candida kefyr	Candida kefyr	ATCC 4135	3.33E+03
Candida famata	Candida famata	ATCC 20278	7.77E+02
Candida famata	Candida famata	ATCC 60229	6.99E+03
Candida dubliniensis	Candida dubliniensis	ATCC MYA-578	3.16E+03
Candida dubliniensis	Candida dubliniensis	ATCC MYA-577	3.16E+03
Candida glabrata	Candida glabrata	ATCC 15545	9.99E+03
Candida glabrata	Candida glabrata	ATCC 15126	1.00E+04
Candida krusei	Candida krusei	ATCC 6258	9.83E+03
Candida krusei	Candida krusei	ATCC 28870	2.95E+04
Candida guilliermondii	Candida guilliermondii	ATCC 22017	3.33E+03
Candida guilliermondii	Candida guilliermondii	ATCC 34134	1.00E+04
Candida lipolytica	Candida lipolytica	ATCC 20460	3.18E+04
Candida lipolytica	Candida lipolytica	ATCC 20177	3.19E+04
Candida lusitaniae	Candida lusitaniae	ATCC 42720	1.11E+04
Candida lusitaniae	Candida lusitaniae	ATCC 34449	3.33E+04

Table 1. LIAISON® PLEX BCY Assay Limit of Detection Results Summary

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LIAISON PLEX Target	Organism	Source & ID	ConfirmedLoD (CFU/mL)
Candida haemulonii/duobushaemulonii	Candida haemulonii	CBS 7375	3.51E+03
	Candida duobushaemulonii	CBS 7798	3.51E+03
Candida auris	Candida auris	CBS 10913	3.50E+03
	Candida auris	CBS 12766	3.50E+03
Candida parapsilosis	Candida parapsilosis	ATCC 28474	2.85E+04
	Candida parapsilosis	ATCC 28475	9.50E+03
Candida tropicalis	Candida tropicalis	ATCC 13803	3.51E+03
	Candida tropicalis	ATCC 201380	3.51E+03
Cryptococcus neoformans/gattii	Cryptococcus neoformans	ATCC 208821	9.01E+04
	Cryptococcus gattii	ATCC MYA-4871	9.00E+04

b. Precision/Reproducibility:

Precision/Repeatability

Within-laboratory precision/repeatability for the LIAISON PLEX® BCY Assay was evaluated across a minimum of five non-consecutive days utilizing two operators, two LIAISON PLEX® Systems and one lot of the LIAISON PLEX® BCY Assay cartridges. The targets were randomized so that the target being tested was blinded to the operators performing the testing. Each target panel (Bottle/Ring Positive (RP), Bottle/Ring Positive + 8 hours (RP+8), Negative Blood Matrix (N), and Contrived-negative containing Escherichia coli + 8 hours (CN)) was run in triplicate by each operator for five non-consecutive days, totaling 15 replicates per target per operator.

The results of the within-laboratory precision / repeatability study are shown in Table 2.The results show the repeatability of the LIAISON PLEX® BCY Assay with an overall percent agreement of 100%, meaning the expected results were obtained for all analytes at all test levels across all samples, instruments, operators, and days.

ReportableTarget	Panel	CartridgeLot	Target PositivityOperator 1		Target PositivityOperator 2		95% C.I.Overall	95% C.I.Lower	95% C.I.Upper
			Instrument 1	Instrument 2	Instrument 1	Instrument 2
C. albicans	Ring Positive	1	100% (7/7)	100% (8/8)	100% (6/6)	100% (9/9)	100% (30/30)	88.7%	100%
C. albicans	Ring Positive+8 hours	1	100% (8/8)	100% (7/7)	100% (5/5)	100% (10/10)	100% (30/30)	88.7%	100%
C. albicans	NegativeBlood Matrix	1	0% (0/7)	0% (0/8)	0% (0/8)	0% (0/7)	0% (0/30)	88.7%	100%

Table 2. Within Laboratory Precision / Repeatability Confidence Interval

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ReportableTarget	Panel	Operator 1		Operator 2		Overall	95% C.I.
		Instrument1	Instrument2	Instrument1	Instrument2		Lower	Upper
C. tropicalis	Ring Positive	100% (7/7)	100% (8/8)	100% (6/6)	100% (9/9)	100%(30/30)	88.7%	100%
	Ring Positive+8 hours	100% (8/8)	100% (7/7)	100% (5/5)	100%(10/10)	100%(30/30)	88.7%	100%
	NegativeBlood Matrix	0% (0/7)	0% (0/8)	0% (0/8)	0% (0/7)	0%(0/30)	88.7%	100%
C.neoformans	Ring Positive	100% (7/7)	100% (8/8)	100% (6/6)	100% (9/9)	100%(30/30)	88.7%	100%
	Ring Positive+8 hours	100% (8/8)	100% (7/7)	100% (5/5)	100%(10/10)	100%(30/30)	88.7%	100%
	NegativeBlood Matrix	0% (0/7)	0% (0/8)	0% (0/8)	0% (0/7)	0%(0/30)	88.7%	100%
ContrivedNegative(E. coli)	N/A	0% (0/6)	0% (0/9)	0% (0/9)	0% (0/6)	0%(0/30)	88.7%	100%

Lot-to-lot Reproducibility

Lot-to-lot reproducibility of the LIAISON PLX BCY Assay was evaluated by testing three different lots of LIAISON PLEX BCY Assay cartridges with one operator over five non-consecutive days, and with two runs per lot. The same target panels used for Precision/Repeatability were used for Lot-to-Lot reproducibility. The blinded reproducibility panels were tested in triplicate for each sample type by operator. Results of the Lot-to-Lot reproducibility are summarized below in Table 3. Overall percent agreement for Lot-to-Lot reproducibility was 100%.

Table 3 Lot-to-Lot Reproducibility Confidence Intervals

Reportable	Panel	Cartridge Lot	Target	95% confidence interval
Target			Positivity	Lower	Upper
C. albicans	RP	Lot 1 (051823106ADEVIUO)	100% (15/15)	79.6%	100%
		Lot 2 (032823106ADEVIUO)	100% (15/15)	79.6%	100%
		Lot 3 (061923106ADEVIUO)	100% (15/15)	79.6%	100%
		Overall	100% (45/45)	92.1%	100%
	RP+8	Lot 1 (051823106ADEVIUO)	100% (15/15)	79.6%	100%	Lot 2 (032823106ADEVIUO)	100% (15/15)	79.6%	100%	Lot 3 (061923106ADEVIUO)	100% (15/15)	79.6%	100%	Overall	100% (45/45)	92.1%	100%
			RP+8	Lot 1 (051823106ADEVIUO)	100% (15/15)	79.6%	100%
				Lot 2 (032823106ADEVIUO)	100% (15/15)	79.6%	100%
				Lot 3 (061923106ADEVIUO)	100% (15/15)	79.6%	100%
Overall	100% (45/45)			92.1%	100%

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complexity sim

LIAISON PLEX® Yeast Blood Culture Assay Traditional 510(k) Submission

ReportableTarget	Panel	Cartridge Lot	TargetPositivity	95% confidence interval
Target				Lower	Upper
C. tropicalis	RP	Lot 1 (051823106ADEVIUO)	100% (15/15)	79.6%	100%
		Lot 2 (032823106ADEVIUO)	100% (15/15)	79.6%	100%
		Lot 3 (061923106ADEVIUO)	100% (15/15)	79.6%	100%
		Overall	100% (45/45)	92.1%	100%
C. neoformans	RP+8	Lot 1 (051823106ADEVIUO)	100% (15/15)	79.6%	100%
		Lot 2 (032823106ADEVIUO)	100% (15/15)	79.6%	100%
		Lot 3 (061923106ADEVIUO)	100% (15/15)	79.6%	100%
		Overall	100% (45/45)	92.1%	100%
Negative	RP	Lot 1 (051823106ADEVIUO)	100% (15/15)	79.6%	100%
		Lot 2 (032823106ADEVIUO)	100% (15/15)	79.6%	100%
		Lot 3 (061923106ADEVIUO)	100% (15/15)	79.6%	100%
		Overall	100% (45/45)	92.1%	100%
	RP+8	Lot 1 (051823106ADEVIUO)	100% (15/15)	79.6%	100%
		Lot 2 (032823106ADEVIUO)	100% (15/15)	79.6%	100%
		Lot 3 (061923106ADEVIUO)	100% (15/15)	79.6%	100%
		Overall	100% (45/45)	92.1%	100%
	CN	Lot 1 (051823106ADEVIUO)	0% (0/15)	79.6%	100%
		Lot 2 (032823106ADEVIUO)	0% (0/15)	79.6%	100%
		Lot 3 (061923106ADEVIUO)	0% (0/15)	79.6%	100%
		Overall	0% (0/45)	92.1%	100%
	N	Lot 1 (051823106ADEVIUO)	0% (0/15)	79.6%	100%
		Lot 2 (032823106ADEVIUO)	0% (0/15)	79.6%	100%
		Lot 3 (061923106ADEVIUO)	0% (0/15)	79.6%	100%
		Overall	0% (0/45)	92.1%	100%

Site-to-site Reproducibility

Site-to-site reproducibility of the LIAISON PLEX BCY Assay was evaluated by testing one lot of LIAISON PLEX BCY Assay cartridges with two operators at each of three sites over five nonconsecutive days. Four target panels were prepared and tested across all sites and operators to evaluate site-to-site reproducibility. The same target panels used for Precision/Repeatability and Lot-to-Lot reproducibility were used for Site-to-Site reproducibility. The blinded reproducibility panels were tested in triplicate for each sample type by each operator on each testing day.

Results of the site-to-site reproducibility study are summarized in Table 4. Reproducibility of

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the LIAISON PLEX® BCY Assay across three sites was 99.7%.

Panel Type	Site	Results (% Agreement)	95% C.I.
Ring Positive	Site 1	100% (30/30)	94.0% - 100%
	Site 2	96.7% (29/30)	83.3% - 99.4%
	Site 3	100% (30/30)	88.6% - 100%
	All Sites	98.9% (89/90)	94.0% - 99.8%
Ring Positive + 8 hours	Site 1	100% (30/30)	88.6% - 100%
	Site 2	100% (30/30)	88.6% - 100%
	Site 3	100% (30/30)	88.6% - 100%
	All Sites	100% (90/90)	95.9% - 100%
Negative Blood Matrix	Site 1	100% (30/30)	88.6% - 100%
	Site 2	100% (30/30)	88.6% - 100%
	Site 3	100% (30/30)	88.6% - 100%
	All Sites	100% (90/90)	95.9% - 100%
Contrived Negative	Site 1	100% (30/30)	88.6% - 100%
	Site 2	100% (30/30)	88.6% - 100%
	Site 3	100% (30/30)	88.6% - 100%
	All Sites	100% (90/90)	95.9% - 100%
Overall		99.7% (359/360)	98.4% - 100%

Table 4. LIAISON® PLEX BCY Assay Site to Site Reproducibility Results

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ﻥ Linearity/assay reportable range:
Not applicable. The LIAISON® PLEX Yeast Blood Culture Assay is a qualitative assay.
d. Traceability, Stability, Expected values (controls, calibrators, or methods):

Controls:

Several controls are built into the assay and system to ensure identification of processing errors and to establish validity of test results.

Internal Controls

Each LIAISON® PLEX BCY Assay cartridge includes internal controls to ensure performance of sample preparation, amplification, and detection. Internal control is automatically added to the sample prior to initiation of sample preparation and assesses extraction, nucleic acid recovery, amplification, and detection. Finally, a post-amplification hybridization control serves as an indicator of successful hybridization. Internal control results are reported as Pass or Fail on the printed reports (see the following Table 5 for detailed explanations of each control result). Internal controls must generate a signal above the threshold in each internal reaction for the system to report a valid test result.

Internal ControlResult	Explanation	Suggested Action
Pass	Test was completed and internal controls weresuccessful, indicating that valid results weregenerated.	Review and report result
Fail	One or more internal controls failed.	Repeat test with a newcartridge

Table 5. Interpretation of Controls on the LIAISON® PLEX BCY Assay Report

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

Contrived specimen stability at incubated storage (33°C - 37°C), refrigerated (2°C - 8°C), and frozen (-80°C ± 15) storage was evaluated for use with the LIAISON" PLEX BCY Assay. Two reference panels, each made of three organisms, were tested at concentrations representing bottle positivity. The panels were then stored at incubated, refrigerated, or frozen temperature conditions. Testing occurred at various time points up to 1 month for

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LIAISON PLEX® Yeast Blood Culture Assay Traditional 510(k) Submission the frozen storage, up to 1 month for refrigerated storage, and up to 72 hours for incubated storage. Specimen stability was also evaluated for specimens grown in a continuous blood monitoring system by testing fresh blood bottle ring positive (RP) and blood bottle ring positive plus 12 hours (RP + 12) samples.

The results of this study demonstrated that specimens stored frozen (< -80°C) are stable for up to 1 month, specimens stored refrigerated (2°C - 8°C) are stable for up to 1 month and specimens stored at incubation (33°C - 37°C) are stable for up to 72 hours. Specimens incubated up to 12 hours after bottle ring positive were 100% detected.

Device Stability

A shelf-life study was conducted to evaluate the real-time stability of the LIAISON PLEX BCY Assay at the recommended storage conditions of room temperature (15°C - 30°C). Real-time stability was assessed using three Positive Control panels which each consisted of representative on-panel fungal organisms, and one Negative Control panel which consisted of negative blood matrix. Results of real-time stability demonstrated the LIAISON PLEX BCY Assay is stable for at least 3 months when stored at 15°C - 30°C.

Open-box stability of the LIAISON PLEX BCY Assay was also evaluated by testing four lots of LIAISON PLEX BCY Assay after removal from their foil pouches and stored at room temperature. The same Positive Control panels and Negative Control panel used for real-time stability were used for open-box stability. 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 study was performed to assess tolerance of the LIAISON® PLEX BCY Assay to correctly detect specimens containing fungal organisms that were tested fresh (i.e. unfrozen) which then underwent one or two freeze-thaw cycles and were tested after each freeze-thaw cycle. This was executed by testing three replicates of each target organism at each of the following concentrations: Blood bottle ring positive (RP), Blood bottle ring positive + 8 hours (RP+8) and Blood bottle ring positive at a ten-fold dilution concentration (RP - 10).

Each target demonstrated an overall positive agreement of 100% at all three testing conditions of fresh, 1 freeze-thaw, and 2 freeze-thaws. Data supports the stability of specimens for up to two freeze-thaw cycles.

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LIAISON PLEX® Yeast Blood Culture Assay Traditional 510(k) Submission

e. Growth and Detection Study:
A Growth and Detection study was performed to evaluate expected organism concentrations in blood cultures at bottle positivity (Ring Positive) and eight hours after bottle positivity (RP+8), using one representative strain for each organisms.

A minimum of one ring positive bottle and one 8 hour plus ring positive bottle from each BCY organism were tested in triplicate on the LIAISON PLEX® BCY assay fresh, meaning the sample was retrieved from the automated blood culture system within the specified timeframe and was tested the same day. A minimum of two ring positive bottles and two 8 hour plus ring positive bottles from each BCY organism were tested in triplicate on the LIAISON PLEX® BCY assay either fresh or after being stored frozen at -65°C to -95°C. In addition, one negative blood bottle was tested fresh in triplicate on the LIAISON PLEX® BCY assay. Concentrations shown below in Table 6 represent approximate levels that may be observed in a clinical setting.

Organism	RepresentativeStrain	Testing Condition(RP/ RP+8)	Concentration(CFU/mL)	TargetPositivity
Candida albicans	Candidaalbicans	RP Fresh	2.21E+04	100%
		RP Frozen	4.30E+05	100%
		RP Frozen	8.60E+05	100%
		RP + 8 Fresh	1.83E+06	100%
		RP + 8 Frozen	1.54E+07	100%
		RP + 8 Frozen	6.90E+06	100%
Candida auris	Candida auris	RP Fresh	1.88E+07	100%
		RP Fresh	1.45E+07	100%
		RP Fresh	2.02E+07	100%
		RP + 8 Fresh	5.30E+07	100%
		RP + 8 Frozen	4.20E+07	100%
		RP + 8 Frozen	4.80E+07	100%
Candidadubliniensis	Candidadubliniensis	RP Fresh	1.47E+07	100%
		RP Fresh	1.98E+07	100%
		RP Fresh	3.20E+07	100%
		RP + 8 Fresh	4.20E+07	100%
		RP + 8 Fresh	4.20E+07	100%
		RP + 8 Fresh	5.10E+07	100%
Candida famata	Debarymoycesfabryi	RP Fresh	7.30E+06	100%
		RP Frozen	4.90E+06	100%
		RP Frozen	3.20E+06	100%
		RP + 8 Fresh	1.20E+07	100%
		RP + 8 Frozen	1.80E+07	100%
		RP + 8 Frozen	5.90E+06	100%
Candida glabrata	Candidaglabrata	RP Fresh	8.00E+06	100%
		RP Frozen	3.80E+06	100%
		RP Frozen	6.10E+06	100%
		RP + 8 Fresh	1.44E+08	100%
		RP + 8 Frozen	1.36E+08	100%
		RP + 8 Frozen	1.60E+08	100%

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Organism	RepresentativeStrain	Testing Condition(RP/ RP+8)	Concentration(CFU/mL)	TargetPositivity
Candidaguilliermondii	Meyerozymaguilliermondii	RP Fresh	1.91E+07	100%
		RP Fresh	3.60E+07	100%
		RP Fresh	1.86E+07	100%
		RP + 8 Fresh	3.60E+07	100%
		RP + 8 Fresh	3.80E+07	100%
		RP + 8 Fresh	3.40E+07	100%
Candidahaemulonii/duobushaemulonii	Candidahaemulonisvar.haemulonis	RP Fresh	9.70E+06	100%
		RP Fresh	9.40E+06	100%
		RP Fresh	1.07E+07	100%
		RP + 8 Fresh	3.20E+07	100%
		RP + 8 Fresh	3.50E+07	100%
		RP + 8 Fresh	4.30E+07	100%
Candida kefyr	Candida kefyr	RP Fresh	8.20E+06	100%
		RP Fresh	6.30E+06	100%
		RP Fresh	1.20E+07	100%
		RP + 8 Fresh	2.34E+07	100%
		RP + 8 Fresh	2.07E+07	100%
		RP + 8 Fresh	2.15E+07	100%
Candida krusei	Candida krusei	RP Fresh	1.24E+07	100%
		RP Frozen	1.66E+07	100%
		RP Frozen	2.09E+07	100%
		RP + 8 Fresh	4.00E+07	100%
		RP + 8 Fresh	4.20E+07	100%
		RP + 8 Fresh	3.50E+07	100%
		RP Fresh	2.44E+06	100%
		RP Frozen	2.50E+06	100%
Candida lipolytica	Yarrowialipolytica	RP Frozen	2.42E+06	100%
		RP + 8 Frozen	3.90E+06	100%
		RP + 8 Fresh	4.60E+06	100%
		RP + 8 Fresh	3.80E+06	100%
		RP Fresh	2.23E+07	100%
		RP Frozen	5.10E+07	100%
		RP Frozen	3.50E+07	100%
Candida lusitaniae	Candidalusitaniae	RP + 8 Fresh	1.33E+08	100%
		RP + 8 Fresh	1.22E+08	100%
		RP + 8 Fresh	1.32E+08	100%
		RP Fresh	1.54E+07	100%
		RP Fresh	1.61E+07	100%
		RP Fresh	1.76E+07	100%
Candidaparapsilosis	Candidaparapsilosis	RP + 8 Fresh	4.10E+07	100%
		RP + 8 Fresh	3.90E+07	100%
		RP + 8 Fresh	5.50E+07	100%
		RP Fresh	1.31E+07	100%
		RP Fresh	1.20E+07	100%
		RP Fresh	1.35E+07	100%
Candida tropicalis	Candidatropicalis	RP + 8 Fresh	3.00E+07	100%

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complexity simplit

LIAISON PLEX® Yeast Blood Culture Assay Traditional 510(k) Submission
Organism	RepresentativeStrain	Testing Condition(RP/ RP+8)	Concentration(CFU/mL)	TargetPositivity
		RP + 8 Fresh	3.90E+07	100%
		RP + 8 Fresh	3.30E+07	100%
Cryptococcusneoformans/gattii	Cryptococcusneoformansvar. grubii	RP Fresh	1.84E+06	100%
		RP Fresh	3.40E+06	100%
		RP Fresh	2.09E+06	100%
		RP + 8 Fresh	5.00E+06	100%
		RP + 8 Frozen	5.50E+06	100%
		RP + 8 Frozen	4.40E+06	100%
NBM	NA	Fresh	NA	0%

f. Analytical Reactivity (Inclusivity)

The analytical reactivity (inclusivity) of the LIAISON PLEX BCY Assay was performed to evaluate inclusive detection of multiple strains of each organism, representing all 14 reportable targets of 16 yeast species, for a total of 80 strains. Assay performance at the representative concentration of bottle positivity was assessed with five strains of each organism diluted in Negative Blood Matrix and tested in triplicate. Bottle positivity represents clinically relevant titers of each organism strain and was determined in execution of the Growth & Detection study for the LIAISON PLEX® BCY Assay. The results, presented in the Table 7, demonstrated 100% positivity for each strain.

Reportable Target	Organism Strain	Source ID	Concentration(CFU/mL)	TargetPositivity
Candida albicans	Candida albicans	ATCC 90028	4.4E+05	100% (3/3)
		ATCC 24433	4.4E+05	100% (3/3)
		ATCC 90029	4.4E+05	100% (3/3)
		ATCC MYA-4780	4.4E+05	100% (3/3)
		Zeptometrix 801504	4.4E+05	100% (3/3)
Candida auris	Candida auris	CBS-KNAW 12373	1.5E+07	100% (3/3)
		CBS-KNAW 12767	1.5E+07	100% (3/3)
		CBS-KNAW 12768	1.5E+07	100% (3/3)
		CDC AR-0383	1.5E+07	100% (3/3)
		Zeptometrix 804386	1.5E+07	100% (3/3)
Candida dubliniensis	Candida dubliniensis	ATCC MYA-582	1.5E+07	100% (3/3)
		ATCC MYA-579	1.5E+07	100% (3/3)
		ATCC 44508	1.5E+07	100% (3/3)
		ATCC MYA-2975	1.5E+07	100% (3/3)
		Zeptometrix 801915	1.5E+07	100% (3/3)
Candida famata	Debaryomyces hansenii¹	ATCC 9365	3.2E+06	100% (3/3)
		ATCC 10619	3.2E+06	100% (3/3)
		ATCC 36239	3.2E+06	100% (3/3)
		CBS-KNAW 1961	3.2E+06	100% (3/3)
		CBS-KNAW 14266	3.2E+06	100% (3/3)
Candida glabrata	Candida glabrata	ATCC MYA-2950	3.8E+06	100% (3/3)
Reportable Target	Organism Strain	Source ID	Concentration(CFU/mL)	TargetPositivity
		ATCC 34138	3.8E+06	100% (3/3)
		ATCC 66032	3.8E+06	100% (3/3)
		ATCC 90876	3.8E+06	100% (3/3)
		Zeptometrix 801535	3.8E+06	100% (3/3)
Candida guilliermondii	Meyerozyma guilliermondii	ATCC 56822	1.9E+07	100% (3/3)
Candida guilliermondii	Meyerozyma guilliermondii	ATCC 14242	1.9E+07	100% (3/3)
Candida guilliermondii	Meyerozyma guilliermondii	ATCC 6260	1.9E+07	100% (3/3)
Candida guilliermondii	Meyerozyma guilliermondii	ATCC 90197	1.9E+07	100% (3/3)
Candida guilliermondii	Candida guilliermondii	Zeptometrix 801602	1.9E+07	100% (3/3)
Candida haemulonii/duobushaemulonii	Candida haemulonii	CDC AR-0395	9.4E+06	100% (3/3)
Candida haemulonii/duobushaemulonii	Candida haemulonis	CBS-KNAW 10970	9.4E+06	100% (3/3)
Candida haemulonii/duobushaemulonii	Candida haemulonis	CBS-KNAW 10973	9.4E+06	100% (3/3)
Candida haemulonii/duobushaemulonii	Candida haemulonii var. vulnera	CBS-KNAW 12437	9.4E+06	100% (3/3)
Candida haemulonii/duobushaemulonii	Candida haemulonii var. vulnera	CBS-KNAW 12438	9.4E+06	100% (3/3)
Candida haemulonii/duobushaemulonii		CBS-KNAW 6915	9.4E+06	100% (3/3)
Candida haemulonii/duobushaemulonii		CBS-KNAW 7098	9.4E+06	100% (3/3)
Candida haemulonii/duobushaemulonii	Candida duobushaemulonii	CDC AR-0392	9.4E+06	100% (3/3)
Candida haemulonii/duobushaemulonii	Candida duobushaemulonii	CDC AR-0394	9.4E+06	100% (3/3)
Candida haemulonii/duobushaemulonii	Candida duobushaemulonii	CDC AR-0391	9.4E+06	100% (3/3)
Candida kefyr	Candida kefyr	ATCC 2512	6.3E+06	100% (3/3)
Candida kefyr	Candida kefyr	ATCC 66028	6.3E+06	100% (3/3)
Candida kefyr	Candida kefyr	ATCC 204093	6.3E+06	100% (3/3)
Candida kefyr	Candida kefyr	ATCC 4135	6.3E+06	100% (3/3)
Candida kefyr	Candida kefyr	Zeptometrix 801837	6.3E+06	100% (3/3)
Candida krusei	Candida krusei	ATCC 32196	1.2E+07	100% (3/3)
Candida krusei	Candida krusei	ATCC 14243	1.2E+07	100% (3/3)
Candida krusei	Candida krusei	ATCC 22985	1.2E+07	100% (3/3)
Candida krusei	Candida krusei	ATCC 34135	1.2E+07	100% (3/3)
Candida krusei	Candida krusei	Zeptometrix 801536	1.2E+07	100% (3/3)
Candida lipolytica	Candida lipolytica	ATCC 8662	2.4E+06	100% (3/3)
Candida lipolytica	Yarrowia lipolytica	ATCC 201242	2.4E+06	100% (3/3)
Candida lipolytica	Yarrowia lipolytica	ATCC 90812	2.4E+06	100% (3/3)
Candida lipolytica	Yarrowia lipolytica	ATCC MYA-2613	2.4E+06	100% (3/3)
Candida lipolytica	Yarrowia lipolytica	ATCC 32338	2.4E+06	100% (3/3)
Candida lusitaniae	Candida lusitaniae	ATCC 200953	2.2E+07	100% (3/3)
Candida lusitaniae	Candida lusitaniae	CBS-KNAW 4870	2.2E+07	100% (3/3)
Candida lusitaniae	Candida lusitaniae	ATCC 66035	2.2E+07	100% (3/3)
Candida lusitaniae	Clavispora lusitaniae	CBS-KNAW 6936	2.2E+07	100% (3/3)
Candida lusitaniae	Clavispora lusitaniae	Zeptometrix 801603	1.9E+072	100% (3/3)
Candida parapsilosis	Candida parapsilosis	ATCC 34136	1.5E+07	100% (3/3)
Candida parapsilosis	Candida parapsilosis	ATCC 96137	1.5E+07	100% (3/3)
Reportable Target	Organism Strain	Source ID	Concentration(CFU/mL)	TargetPositivity
		ATCC 200954	1.5E+07	100% (3/3)
		ATCC 38291	1.5E+07	100% (3/3)
		Zeptometrix 801537	1.5E+07	100% (3/3)
Candida tropicalis	Candida tropicalis	ATCC MYA-2734	1.2E+07	100% (3/3)
		ATCC 1369	1.2E+07	100% (3/3)
		ATCC 90874	1.2E+07	100% (3/3)
		ATCC 18807	1.2E+07	100% (3/3)
		Zeptometrix 801538	1.2E+07	100% (3/3)
Cryptococcusneoformans/gattii	Cryptococcus neoformansvar. grubii	ATCC 14116	1.8E+06	100% (3/3)
	Cryptococcus neoformans	ATCC 90112	1.8E+06	100% (3/3)
		ATCC MYA-4564	1.8E+06	100% (3/3)
		ATCC MYA-4566	1.8E+06	100% (3/3)
		Zeptometrix 801803	1.8E+06	100% (3/3)
	Cryptococcus gattii	ATCC MYA-4563	1.8E+06	100% (3/3)
		ATCC MYA-4873	1.8E+06	100% (3/3)
		ATCC MYA-4560	1.8E+06	100% (3/3)
		ATCC MYA-4094	1.8E+06	100% (3/3)
	Cryptococcus gattii	Zeptometrix 801917	1.8E+06	100% (3/3)

Table 7. LIAISON PLEX® BCY Inclusivity Summary

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LIAISON PLEX® Yeast Blood Culture Assay Traditional 510(k) Submission

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complexity simplified.

¹Debaryomyces hansenii is a synonymous taxon name for Candida famata.

2 The stock concentration of Clavispora lusitaniae (Zeptometrix 801603) was not concentrative bottle positivity concentration. This prepared as stock material diluted 1:1 in Negative Blood Matrix which is allowed per protocol directive.

Predicted (in silico) Reactivity (Inclusivity) Results

In-silico inclusivity analyses of the assay oligo sequences were performed against sequences available in the GenBank nt database as of December 30, 2023. The inclusivity analyses involved assessing the precent 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. A summary of in-silico inclusivity analysis results are summarized below in Table 8.

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complexity simplified.

Reportable Target	Inclusive Organism/Target	Total # SequencesinAlignment	# Sequences withPercent OligoIdentity≥ 90%	PredictedInclusivityPercentage(%)
Candida albicans	Candida albicans	181 *	181	100
Candida auris	Candida auris	286	286	100
Candida dubliniensis	Candida dubliniensis	13 *	13	100
Candida famata	Candida famata	32 *	32	100
Candida glabrata	Candida glabrata	206	206	100
Candida guilliermondii	Candida guilliermondii	24 *	24	100
Candida haemulonii/duobushamulonii	Candida haemulonii	17 *	17	100
	Candida duobushamulonii	9 *	9	100
Candida kefyr	Candida kefyr	30 *	30	100
Candida krusei	Candida krusei	48 *	48	100
Candida lipolytica	Candida lipolytica	82 *	82	100
Candida lusitaniae	Candida lusitaniae	75 *	75	100
Candida parapsilosis	Candida parapsilosis	59 *	59	100
Candida tropicalis	Candida tropicalis	86 *	85	99
Cryptococcusneoformans/gattii	Cryptococcus neoformans	3243	3243	100
	Cryptococcus gattii	1236	1236	100

Table 8. In-silico Analysis Results

Includes WGS (whole genome shotgun) sequences.

g. Analytical Specificity (Exclusivity)

Cross-Reactivity:

A Cross-Reactivity study was performed to evaluate the LIAISON PLEX® BCY Assay's analytical specificity through the detection of off-panel and potentially cross-reactive organisms, including those phylogenetically related to the on-panel organisms and organisms likely to be present in blood culture samples.

Out of the 40 off-panel bacterial species tested, there was no cross-reactivity with any of the on-panel organisms. Out of the 37 off-panel yeast species tested, 35 organisms had no crossreactivity with on-panel organisms. Yarrowia deformans (NRRL Y-63659) cross-reacted and had 100% detection for the BCY target Candida lipolytica when tested at a concentration of 1.0E+07 CFU/mL. Candida pseudohaemulonii (CBS-KNAW 10004) cross-reacted and had 100% detection for the BCY target Candida haemulonii/duobushaemulonii when tested at 1.0E+07 CFU/mL.

One bacterial organism, Klebsiella pneumoniae (ATCC-BAA 2146), had 11% positivity (1 of 9) for the on-panel organisms Candida albicans and Candida dubliniensis at a concentration of 1.0E+08 CFU/mL. Candida pseudohaemulonii (CBS-KNAW 10004) also had 11% detection (1 of 9) for the BCY target Candida lusitaniae when tested at 1.0E+07 CFU/mL. Trichosporon asteroides (CBS-KNAW 6183) had 50% positivity (3 of 6) for Candida glabrata and 33% (2 of 6) positivity for Candida haemulonii/duobushaemulonii at a concentration of 1.0E+07 CFU/mL. In-silico analysis and wet testing support that cross-reactivity is not expected to occur with these targets.

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Refer to the Tables below which summarizes cross reactivity testing performed with Bacteria strains (Table 9) and Yeast strains (Table 10).

Organism	ConcentrationTested (CFU/mL)	Source &Source ID	Positivity % (Organism)
Acinetobacter baumannii	1.0E+08	IHMA 128307	0% (0/3)
Acinetobacter Iwoffii	1.0E+08	ATCC 15309	0% (0/3)
Aerococcus viridans	1.0E+08	ATCC 700406	0% (0/3)
Bacillus cereus	1.0E+08	ATCC 14579	0% (0/3)
Bacteroides fragilis	1.0E+08	ATCC 25285	0% (0/3)
Bordetella pertussis	1.0E+08	ATCC 9797	0% (0/3)
Cutibacterium (Propionibacterium) acnes	1.0E+08	ATCC 33179	0% (0/3)
Citrobacter freundii	1.0E+08	ATCC 8090	0% (0/3)
Clostridium perfringens	1.0E+08	ATCC 13124	0% (0/3)
Corynebacterium striatum	1.0E+08	ATCC 43735	0% (0/3)
Enterobacter aerogenes	1.0E+08	ATCC 35029	0% (0/3)
Enterococcus avium	1.0E+08	ATCC 14025	0% (0/3)
Enterobacter cloacae	1.0E+08	ATCC 35030	0% (0/3)
Escherichia coli	1.0E+08	NCTC 13846	0% (0/3)
Enterococcus faecalis	1.0E+08	ATCC 29212	0% (0/3)
Enterococcus faecium	1.0E+08	ATCC 700221	0% (0/3)
Eggerthella lenta	1.0E+08	ATCC 25559	0% (0/3)
Klebsiella oxytoca	1.0E+08	ATCC 43165	0% (0/3)
Klebsiella pneumoniae	1.0E+08	ATCC-BAA2146	11% (C. albicans) (1/9)11% (C. dubliniensis) (1/9)
Listeria monocytogenes	1.0E+08	ATCC 19115	0% (0/3)
Lactobacillus rhamnosus	1.0E+08	ATCC 53103	0% (0/3)
Micrococcus luteus	8.9E+06	ATCC 10054	0% (0/3)
Morganella morganii	1.0E+08	ATCC 25830	0% (0/3)
Pseudomonas aeruginosa	1.0E+08	IHMA 576602	0% (0/3)
Prevotella denticola	1.0E+08	BEI ResourcesHM-1173	0% (0/3)
Proteus mirabilis	1.0E+08	ATCC 12453	0% (0/3)
Streptococcus agalactiae	1.0E+08	ATCC 12401	0% (0/3)
Streptococcus anginosus	1.0E+08	ATCC 33397	0% (0/3)
Staphylococcus aureus	1.0E+08	ATCC 25923	0% (0/3)
Salmonella enterica	1.0E+08	ATCC 9993	0% (0/3)
Staphylococcus epidermidis	1.0E+08	ATCC 700567	0% (0/3)
Staphylococcus hominis	1.0E+08	ATCC 27844	0% (0/3)
Staphylococcus intermedius	1.0E+08	ATCC 29663	0% (0/3)
Staphylococcus lugdunensis	1.0E+08	ATCC 43809	0% (0/3)
Stenotrophomonas maltophilia	8.9E+07	ATCC 17666	0% (0/3)
Serratia marcescens	1.0E+08	NCTC 13920	0% (0/3)
Organism	ConcentrationTested (CFU/mL)	Source &Source ID	Positivity % (Organism)
Streptococcus mitis	1.0E+08	ATCC 15914	0% (0/3)
Streptococcus pneumoniae	1.0E+08	ATCC 6315	0% (0/3)
Streptococcus pyogenes	1.0E+08	ATCC 12964	0% (0/3)
Staphylococcus saprophyticus	1.0E+08	ATCC 15305	0% (0/3)

Table 9. LIAISON PLEX® BCY Assay Analytical Specificity – Cross Reactivity Bacteria Summary

Confidential & Restricted

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LIAISON PLEX® Yeast Blood Culture Assay Traditional 510(k) Submission

Table 10. LIAISON PLEX® BCY Assay Analytical Specificity – Cross Reactivity Yeast Summary

Organism	ConcentrationTested (CFU/mL)	Source & SourceID	Positivity % (Organism)
Aspergillus fumigatus	1.0E+07	ATCC 1022	0% (0/3)
Acremonium kiliense	1.0E+07	ATCC 20337	0% (0/3)
Candida bracarensis	1.0E+07	JH 47	0% (0/3)
Candida carpophila	1.0E+07	CBS-KNAW 5256	0% (0/3)
Candida inconspicua	1.0E+07	NRRL Y-2029	0% (0/3)
Candida intermedia	1.0E+07	ATCC 14439	0% (0/3)
Candida metapsilosis	1.0E+07	NRRL Y-48470	0% (0/3)
Candida nivariensis	1.0E+07	CBS-KNAW 9983	0% (0/3)
Candida orthopsilosis	1.0E+07	ATCC 20504	0% (0/3)
Candida pseudohaemulonii	1.0E+07	CBS-KNAW 10004	100% (C. haemulonii) (9/9)11% (C. lusitaniae) (1/9)
Candida pseudohaemulonii	1.0E+06	CBS-KNAW 10004	100% (C. haemulonii) (3/3)
Candida pseudohaemulonii	1.0E+05	CBS-KNAW 10004	100% (C. haemulonii) (3/3)
Candida pseudohaemulonii	1.0E+04	CBS-KNAW 10004	100% (C. haemulonii) (3/3)
Candida pseudohaemulonii	1.0E+03	CBS-KNAW 10004	33% (C. haemulonii) (1/3)
Candida pseudohaemulonii	1.0E+02	CBS-KNAW 10004	0% (0/3)
Candida rugosa	1.0E+07	NRRL Y-95	0% (0/3)
Candida sake	1.0E+07	NRRL Y-1622	0% (0/3)
Candida solani	1.0E+07	NRRL Y-2224	0% (0/3)
Candida utilis	1.0E+07	ATCC 9950	0% (0/3)
Exophiala lecanii-corni	1.0E+07	ATCC 12734	0% (0/3)
Filobasidium elegans	1.0E+07	NRRL Y-6486	0% (0/3)
Filobasidium globisporum	1.0E+07	NRRL Y-17828	0% (0/3)
Kluyveromyces lactis	1.0E+07	ATCC 24207	0% (0/3)
Kodamaea ohmeri	1.0E+07	NRRL Y-1932	0% (0/3)
Meyerozyma caribbica	1.0E+07	NRRL Y-27274	0% (0/3)
Malassezia furfur	1.0E+07	ATCC 14521	0% (0/3)
Malassezia globosa	1.0E+07	ATCC-MYA 4612	0% (0/3)
Metschnikowia pulcherrima	1.0E+07	ATCC 22032	0% (0/3)
Malassezia restricta	1.0E+07	ATCC-MYA 4611	0% (0/3)
Malassezia sympodialis	1.0E+07	ATCC 96803	0% (0/3)
Mucor velutinosus	1.0E+07	ATCC-MYA 4766	0% (0/3)
Pichia fermentans	1.0E+07	NRRL Y-1619	0% (0/3)
Pichia norvegensis	1.0E+07	NRRL YB-3904	0% (0/3)

Confidential & Restricted

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complexity simplified.

Organism	ConcentrationTested (CFU/mL)	Source & SourceID	Positivity % (Organism)
Rhodotorula mucilaqinosa	1.0E+07	ATCC 66034	0% (0/3)
Saccharomyces cerevisiae	1.0E+07	ATCC 18824	0% (0/3)
Scedosporium prolificans	1.0E+07	ATCC 64913	0% (0/3)
Sporidiobolus salmonicolor	1.0E+07	NRRL Y-5483	0% (0/3)
Sporothrix schenckii	1.0E+07	ATCC 58251	0% (0/3)
Trichosporon asteroides	1.0E+07	CBS-KNAW 6183	50% (C. glabrata) (3/6)33% (C. haemulonii) (2/6)
Talaromyces marneffei	1.45E+06spores/mL	ATCC 18224	0% (0/3)
Wickerhamomyces anomalus	1.0E+07	ATCC 10262	0% (0/3)
Yarrowia deformans	1.0E+07	NRRL Y-63659	100% (C. lipolytica) (9/9)
Yarrowia deformans	1.0E+06	NRRL Y-63659	100% (C. lipolytica) (3/3)
Yarrowia deformans	1.0E+05	NRRL Y-63659	100% (C. lipolytica) (3/3)
Yarrowia deformans	1.0E+04	NRRL Y-63659	0% (0/3)

In silico cross-reactivity

In silico exclusivity assessment was performed using sequences available in the GenBank nt database as of December 28, 2023. Based on analysis of the sequences available in the GenBank nt database, the following potential cross-reactivity scenarios are predicted:

The Candida lipolytica oligo designs are predicted to detect Yarrowia deformans strains ● resulting in false positive results.
. The Candida haemulonii/duobushamulonii oligo designs are predicted to detect Candida pseudohaemulonii strains resulting in false positive results.

The potential cross-reactive organisms assessed for in silico exclusivity analysis are provided below in Table 11.

	Off-Panel Organisms
On-Panel Organisms	Bacteria	Fungi
Candida albicans	Acinetobacter baumanii	Acremonium kiliense
Candida auris	Acinetobacter Iwoffii	Aspergillus fumigatus
Candida dubliniensis	Aerococcus viridans	Candida bracarensis
Candida duobushamulonii	Bacillus cereus	Candida carpophila
Candida famata	Bacteroides fragilis	Candida inconspicua
Candida glabrata	Bordetella pertussis	Candida intermedia
Candida guilliermondii	Citrobacter freundii	Candida lambica
Candida haemulonii	Clostridium perfringens	Candida metapsilosis
Candida kefyr	Corynebacterium striatum	Candida nivariensis
Candida krusei	Cutibacterium (Propionibacterium) acnes	Candida norvegensis
Candida lipolytica	Eggerthella lenta	Candida orthopsilosis

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

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complexity simplif

LIAISON PLEX® Yeast Blood Culture Assay Traditional 510(k) Submission

	Off-Panel Organisms
On-Panel Organisms	Bacteria	Fungi
Candida lusitaniae	Enterobacter aerogenes	Candida pelliculosa
Candida parapsilosis	Enterobacter cloacae	Candida pseudohaemulonii
Candida tropicalis	Enterococcus avium	Candida sake
Cryptococcus gattii	Enterococcus faecalis	Candida utilis
Cryptococcus neoformans	Enterococcus faecium	Diutina (Candida) rugosa
	Escherichia coli	Exophiala jeanselmei
	Klebsiella oxytoca	Filobasidium elegans
	Klebsiella pneumoniae	Filobasidium globisporum
	Lactobacillus rhamnosus	Fusarium solani
	Listeria monocytogenes	Kluyveromyces lactis
	Micrococcus luteus	Kodamaea ohmeri
	Morganella morganii	Malassezia furfur
	Prevotella denticola	Malassezia globose
	Proteus mirabilis	Malassezia restricta
	Pseudomonas aeruginosa	Malassezia sympodialis
	Salmonella enterica (Typhi)	Metschnikowia (Candida) pulcherrima
	Serratia marcescens	Meyerozyma caribbica (Candida fermentati)
	Staphylococcus aureus	Mucor velutinosus
	Staphylococcus epidermidis	Penicillium marneffei
	Staphylococcus hominis	Rhodotorula mucilaginosa
	Staphylococcus intermedius	Saccharomyces cerevisiae
	Staphylococcus lugdunensis	Scedosporium prolificans
	Staphylococcus saprophyticus	Sporidiobolus salmonicolor
	Stenotrophomonas maltophilia	Sporothrix schenckii
	Streptococcus agalactiae	Trichosporon spp.
	Streptococcus anginosus	Yarrowia deformans
	Streptococcus mitis	Protozoa
	Streptococcus pneumoniae	Plasmodium falciparum
	Streptococcus pyogenes	Trypanosoma cruzi

h. Interference

Microbial Interference

The impact of nine potentially interfering microbial organisms commonly found in blood culture samples were tested in the presence of on-panel organisms. C. glabrata, and C. parapsilosis were selected as the three representative on-panel organisms used throughout this study. Each potentially interfering organism was tested at a high concentration of ≥ 1.00+E08 CFU/mL for bacteria, in the presence of the on-panel organisms which were tested at low concentrations (ring positive), which were determined during the Growth and Detection Study. Table 12 summarizes the results from the Microbial Interference studies.

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LIAISON PLEX® Yeast Blood Culture Assay Traditional 510(k) Submission Table 12. LIAISON PLEX® BCY Microbial Interference Summary

Table 12. LIAISON PLEX® BCY Microbial Interference Summary
Off-Panel High ConcentrationInterfering Microbe	On-Panel LowConcentration Target	TargetPositivity
Escherichia coli(1.0E+08 CFU/mL)	Candida albicans(4.4E+05 CFU/mL)	100% (3/3)
	Candida glabrata(3.8E+06 CFU/mL)	100% (3/3)
	Candida parapsilosis(1.5E+07 CFU/mL)	100% (3/3)
Staphylococcus aureus(1.0E+08 CFU/mL)	Candida albicans(4.4E+05 CFU/mL)	100% (3/3)
	Candida glabrata(3.8E+06 CFU/mL)	100% (3/3)
	Candida parapsilosis(1.5E+07 CFU/mL)	100% (3/3)
Klebsiella pneumoniae(1.0E+08 CFU/mL)	Candida albicans(4.4E+05 CFU/mL)	100% (3/3)
	Candida glabrata(3.8E+06 CFU/mL)	100% (3/3)
	Candida parapsilosis(1.5E+07 CFU/mL)	100% (3/3)
Pseudomonas aeruginosa(1.0E+08 CFU/mL)	Candida albicans(4.4E+05 CFU/mL)	100% (3/3)
	Candida glabrata(3.8E+06 CFU/mL)	100% (3/3)
	Candida parapsilosis(1.5E+07 CFU/mL)	100% (3/3)
Enterococcus faecalis(1.0E+08 CFU/mL)	Candida albicans(4.4E+05 CFU/mL)	100% (3/3)
	Candida glabrata(3.8E+06 CFU/mL)	100% (3/3)
	Candida parapsilosis(1.5E+07 CFU/mL)	100% (3/3)
Staphylococcus epidermidis(1.0E+08 CFU/mL)	Candida albicans(4.4E+05 CFU/mL)	100% (3/3)
	Candida glabrata(3.8E+06 CFU/mL)	100% (3/3)
	Candida parapsilosis(1.5E+07 CFU/mL)	100% (3/3)
Enterococcus faecium(1.0E+08 CFU/mL)	Candida albicans(4.4E+05 CFU/mL)	100% (3/3)
	Candida glabrata(3.8E+06 CFU/mL)	100% (3/3)
	Candida parapsilosis(1.5E+07 CFU/mL)	100% (3/3)
Off-Panel High ConcentrationInterfering Microbe	On-Panel LowConcentration Target	TargetPositivity
(1.0E+08 CFU/mL)	(4.4E+05 CFU/mL)
(1.0E+08 CFU/mL)	Candida glabrata(3.8E+06 CFU/mL)	100% (3/3)
(1.0E+08 CFU/mL)	Candida parapsilosis(1.5E+07 CFU/mL)	100% (3/3)
Streptococcus pneumoniae(1.0E+08 CFU/mL)	Candida albicans(4.4E+05 CFU/mL)	100% (3/3)
Streptococcus pneumoniae(1.0E+08 CFU/mL)	Candida glabrata(3.8E+06 CFU/mL)	100% (3/3)
Streptococcus pneumoniae(1.0E+08 CFU/mL)	Candida parapsilosis(1.5E+07 CFU/mL)	100% (3/3)

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LIAISON PLEX® Yeast Blood Culture Assay Traditional 510(k) Submission

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LIAISON PLEX® Yeast Blood Culture Assay Traditional 510(k) Submission

Interfering Substances:

An Interfering Substance study was performed to evaluate non-microbial interference of 18 substances which may be present during collection or within clinical blood samples using the LIAISON PLEX® BCY Assay. Two positive panels containing three (3) on-panel organisms each (C. albicans, C. tropicalis, C. neoformans and C. glabrata, C. guilliermondii, and C. kefyr) and negative blood matrix were used to test each interfering substance at clinically relevant concentrations. The potentially interfering substances and their testing concentrations are listed in Table 15, the substances do not interfere with the LIAISON PLEX BCY Assay. All positive panel results were 100% positive. However, Fluconazole at the testing concentration of 25 mg/L showed interference and resulted in a false negative for C. albicans.At the testing concentrations listed in Table 13, the substances do not interfere with the LIAISON PLEX BCY Assay. All positive panel results were 100% positive. However, Fluconazole at the testing concentration of 25 mg/L showed interference and resulted in a false negative for C. albicans.

Interfering Substance	Interfering SubstanceConcentration
Unconjugated Bilirubin	20 mg/dL
Conjugated Bilirubin	20 mg/dL
Hemoglobin	14 g/L
y-globulin	6 g/dL
SodiumPolyanetholsulfonate	0.25% w/v
Amoxicillin clavulanate	3.5 µg/mL
Amphotericin B	2 µg/mL
Caspofungin	5 µg/mL
Ceftriaxone	0.23 mg/mL

Table 13 - List of Potentially Interfering Substances

Interfering Substance	Interfering Substance Concentration
Ciprofloxacin	3 mg/L
Fluconazole	25 mg/L
	8.3 mg/L
Flucytosine	90 µg/mL
Gentamicin sulfate	3 µg/mL
Heparin	0.9 U/mL
Imipenem	83 µg/mL
Tetracycline	5 mg/L
Vancomycin	30 mg/L
Intralipid/Triglycerides	3000 mg/dL
Controls	N/A
0.9% NaCl Solvent Blank	N/A

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LIAISON PLEX® Yeast Blood Culture Assay Traditional 510(k) Submission

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Competitive Interference/Co-infection:

Competitive inhibition of the LIAISON PLEX® BCY was assessed by testing six pairings of clinically prevalent co-infections. A single pairing consisted of one target at a high concentration with another target at a low concentration targets were tested at a concentration representative of Ring Positivity, as determined during the Growth and Detection study. All high concentration targets were tested at a concentration representative of Ring Positivity + 8 hours, as determined during the Growth and Detection study. Testing of each combination was performed in triplicate.

On-Panel HighConcentration Target	High ConcentrationTarget Positivity	On-Panel LowConcentration Target	Low ConcentrationTarget Positivity
Candida parapsilosis(5.5E+07 CFU/mL)	100% (3/3)	Candida albicans(4.4E+05 CFU/mL)	100% (3/3)
Candida parapsilosis(5.5E+07 CFU/mL)	100% (3/3)	Candida glabrata(3.8E+06 CFU/mL)	100% (3/3)
Candida glabrata(1.6E+08 CFU/mL)	100% (3/3)	Candida parapsilosis(1.5E+07 CFU/mL)	100% (3/3)
Candida glabrata(1.6E+08 CFU/mL)	100% (3/3)	Candida albicans(4.4E+05 CFU/mL)	100% (3/3)
Candida albicans(1.5E+07 CFU/mL)	100% (3/3)	Candida glabrata(3.8E+06 CFU/mL)	100% (3/3)
Candida albicans(1.5E+07 CFU/mL)	100% (3/3)	Candida parapsilosis(1.5E+07 CFU/mL)	100% (3/3)

Table 14. LIAISON PLEX® BCY Co-Infection Summary

Carry-Over/Cross-Contamination:

Carry-over and cross contamination for the LIAISON PLEX® BCY Assay was evaluated by testing positive and negative samples in an alternating series. Two operators tested 30 high concentration C. lusitaniae positive samples and 30 negative samples across two instruments over the course of two days. The samples were loaded into cartridges alternating between positive and negative samples, six cartridges at a time using sample prep trays. The six cartridges were loaded into a LIAISON PLEX® instrument in the same order they were loaded with sample. The instruments set-ups made it so the sample loaded and ran on each blade alternated between positive samples and negative samples for all runs executed in this study. The results demonstrated 100% agreement between expected and observed results, indicating that no carry-over or cross contamination occurred between and during runs.

i. Assay Cut-off

The specific assay parameters for the LIAISON PLEX® BCY Assay are considered confidential and proprietary.

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2. Comparison Studies:

Method comparison with predicate device: a.
Refer to Section 3 Clinical Performance.
b. Matrix Comparison: Testing of Blood Culture Bottle Types / Matrix Equivalency
The LIAISON PLEX " BCY Assay was evaluated to confirm equivalent performance for target detection in twelve different blood bottle matrixes from three different blood culture systems (BacT/Alert, BACTEC, and VersaTREK). The matrix was tested with negative blood matrix, two positive control panels, and with representative bacteria strains. Positive Control Panel 1 was comprised of Candida albicans, Cryptococcus neoformans, and Candida tropicalis. Positive Control Panel 2 was comprised of Candida glabrata, Candida guilliermondii, and Candida kefyr. The Positive Control Panels were tested at concentration representing blood culture bottle positivity, as determined during the Growth and Detection study. The bacteria strains used to test the assay were Acinetobacter baumannii, Escherichia coli, Klebsiella pneumonia, Straphylococcus aureus, and Pseudomonas aeruginosa. Bacteria strains were all tested at the concentration of 1.00E+08 CFU/mL. A negative sample, Negative Blood Matrix, was also tested. A summary of blood bottle equivalency results is explained in Table 15.

Manufacturer	BottleManufacturerPart Number	BottleName	Bottle Lot	Percent Positivity
				NBM	PositiveControl11	PositiveControl22	OffPanelTargets3
ThermoScientific	7106-44	VersaTrekRedox 1	593815	0%(0/5)	100%(5/5)	100%(5/5)	0%(0/10)
			593817	0%(0/5)	100%(5/5)	100%(5/5)	0%(0/10)
ThermoScientific	7107-44	VersaTrekRedox 2	576419	0%(0/5)	100%(5/5)	100%(5/5)	0%(0/10)
			626823	0%(0/5)	100%(5/5)	100%(5/5)	0%(0/10)
Becton,Dickinson,and Company(BD)	442022	Bactec PlusAnaerobic/F	3010406	0%(0/5)	100%(5/5)	100%(5/5)	0%(0/10)
			3041161	0%(0/5)	100%(5/5)	100%(5/5)	0%(0/10)

4 This percent positivity reflects the percent positive control 1, which includes Candida albicans, Candida tropicalis, and Cryptococcus neoformans.

2 This percent positivity reflects the percent positive control 2, which includes Condida globrato, Candida guilliermondii, and Candida kefyr.

3 This percent positivity reflects the percent positivity of all replicates from the 5 bacteria strains tested.

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LIAISON PLEX® Yeast Blood Culture Assay Traditional 510(k) Submission

Manufacturer	BottleManufacturerPart Number	BottleName	Bottle Lot	Percent Positivity
				NBM	PositiveControl11	PositiveControl22	OffPanelTargets3
	442024	Bactec PlusStandardAnaerobic/F	2186992	0%(0/5)	100%(5/5)	100%(5/5)	0%(0/10)
		Bactec PlusStandardAnaerobic/F	2326552	20%(1/5)	100%(5/5)	100%(5/5)	0%(0/10)
	442021	BactecLytic/10Anaerobic/F	2227861	0%(0/5)	100%(5/5)	100%(5/5)	0%(0/10)
		BactecLytic/10Anaerobic/F	3046048	0%(0/5)	100%(5/5)	100%(5/5)	0%(0/10)
	442023	Bactec PlusAerobic/F	2178710	0%(0/5)	100%(5/5)	100%(5/5)	0%(0/10)
		Bactec PlusAerobic/F	3041879	0%(0/5)	100%(5/5)	100%(5/5)	0%(0/10)
	442020	Bactec PedsPlus	2263255	0%(0/5)	100%(5/5)	100%(5/5)	0%(0/10)
		Bactec PedsPlus	3067576	0%(0/5)	100%(5/5)	100%(5/5)	0%(0/10)
	442027	BactecStandard/10Aerobic	2227933	0%(0/5)	100%(5/5)	100%(5/5)	0%(0/10)
		BactecStandard/10Aerobic	3060893	0%(0/5)	100%(5/5)	100%(5/5)	0%(0/10)
BioMérieux	259789	BACT/AlertSA	0001059400	0%(0/5)	100%(5/5)	100%(5/5)	0%(0/10)
			0001059708	0%(0/5)	100%(5/5)	100%(5/5)	0%(0/10)
	410852	BACT/AlertFN Plus	0004059160	0%(0/5)	100%(5/5)	100%(5/5)	0%(0/10)
			0004059844	0%(0/5)	100%(5/5)	100%(5/5)	0%(0/10)
	259790	BACT/AlertSN	0001059860	0%(0/5)	100%(5/5)	100%(5/5)	0%(0/10)
			0001059900	0%(0/5)	100%(5/5)	100%(5/5)	0%(0/10)
	410853	BACT/AlertPE Plus	0004101300	0%(0/5)	100%(5/5)	100%(5/5)	0%(0/10)

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complexity simplified.

Manufacturer	BottleManufacturerPart Number	BottleName	Bottle Lot	Percent Positivity
				NBM	PositiveControl11	PositiveControl22	OffPanelTargets3
			0004101532	0%(0/5)	100%(5/5)	100%(5/5)	0%(0/10)

3. Clinical Performance:

A multi-site clinical study established the diagnostic accuracy of the LIAISON PLEX® BCY Assay for the detection and identification of multiple potentially pathogenic fungal organisms in positive blood culture from blood culture media identified as positive by a continuous monitoring blood culture system and which contain fungal organisms as determined by Gram Stain. The clinical performance of the LIAISON PLEX BCY Assay was evaluated using a combination of prospectively collected de-identified remnant samples, preselected positive samples, and contrived samples.

A total of 3447 unique prospectively collected specimens were evaluated for their eligibility across four geographically diverse US clinical sites. Of these, 69 (1 specimen was excluded due to inconclusive gram stain result) prospective specimens that met the pre-determined inclusion criteria and exhibited yeast morphology following gram stain were enrolled in the study. Clinical runs and re-runs using the LIAISON PLEX® BCY Assay were tested on the LIAISON PLEX® System by trained operators at four sites. Prospective specimen testing occurred between June 2023 and October 2023.

As all targets exhibited low prevalence rates in the prospective specime specimen set was supplemented with pre-selected and contrived specimens. The 63 pre-selected specimens were remnant, de-identified specimens sourced from 6 different sites/vendors in the United States. The pre-selected specimens were characterized by an FDA cleared molecular assay prior to enrollment in the study. The pre-selected specimens were tested in a randomized, blinded manner with negative specimens at one site during October 2023.

Out of the 132 clinical specimens included in the prospective and pre-selected study analysis, 130 (98.5%) generated valid BCY Assay results (i.e., Detected or Not Detected) on the first attempt. Two (1.5%) specimens with initial invalid results generated valid BCY results after a single retest. 132 specimens generated valid BCY results for a final success rate of 100.0% (132/132).

Table 16 provides a summary of the general demographic information of the 69 prospectively collected specimens that were included in the clinical study.

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LIAISON PLEX® Yeast Blood Culture Assay Traditional 510(k) Submission Table 16 - Demographic Information for Prospectively collected specimens

Gender	Site 01	Site 02	Site 03	Site 04	All Sites
Male	24(57.1%)	6(54.5%)	5(45.5%)	1(20.0%)	36(52.2%)
Female	17(40.5%)	5(45.5%)	6(54.5%)	4(80.0%)	32(46.4%)
Gender Unknown	1(2.4%)	0(0.0%)	0(0.0%)	0(0.0%)	1(1.4%)
Total	42(100.0%)	11(100.0%)	11(100.0%)	5(100.0%)	69(100.0%)
Age (years)
0-1	2(4.8%)	0(0.0%)	0(0.0%)	1(20.0%)	3(4.3%)
>1-5	0(0.0%)	0(0.0%)	0(0.0%)	0(0.0%)	0(0.0%)
>5-21	0(0.0%)	1(9.1%)	0(0.0%)	0(0.0%)	1(1.4%)
>21-65	21(50.0%)	9(81.8%)	8(72.7%)	3(60.0%)	41(59.4%)
>65	18(42.9%)	1(9.1%)	3(27.3%)	1(20.0%)	23(33.3%)
Age Unknown	1(2.4%)	0(0.0%)	0(0.0%)	0(0.0%)	1(1.4%)
Total	42(100.0%)	11(100.0%)	11(100.0%)	5(100.0%)	69(100.0%)
Subject Status
Emergency Room	0(0.0%)	1(9.1%)	4(36.4%)	0(0.0%)	5(7.2%)
Hospitalized	0(0.0%)	10(90.9%)	7(63.6%)	5(100.0%)	22(31.9%)
Status Unknown	42(100.0%)	0(0.0%)	0(0.0%)	0(0.0%)	42(60.9%)
Total	42(100.0%)	11(100.0%)	11(100.0%)	5(100.0%)	69(100.0%)
Blood CultureBottle type
BD BACTEC LyticAnaerobic	0(0.0%)	3(27.3%)	0(0.0%)	0(0.0%)	3(4.3%)
BD BACTEC PlusAerobic	0(0.0%)	8(72.7%)	6(54.5%)	0(0.0%)	14(20.3%)
BD BACTECStandard Aerobic	0(0.0%)	0(0.0%)	5(45.5%)	0(0.0%)	5(7.2%)
BacT/ALERT FAPlus	40(95.2%)	0(0.0%)	0(0.0%)	0(0.0%)	40(58.0%)
BacT/ALERT FNPlus	1(2.4%)	0(0.0%)	0(0.0%)	0(0.0%)	1(1.4%)
BacT/ALERT PFPlus	1(2.4%)	0(0.0%)	0(0.0%)	1(20.0%)	2(2.9%)
BacT/ALERT SAStandard Aerobic	0(0.0%)	0(0.0%)	0(0.0%)	3(60.0%)	3(4.3%)
BacT/ALERT SNStandard Anaerobic	0(0.0%)	0(0.0%)	0(0.0%)	1(20.0%)	1(1.4%)
Bottle Type Total	42(100.0%)	11(100.0%)	11(100.0%)	5(100.0%)	69(100.0%)

Table 17 provides a summary of the general demographic information of the 63 pre-selected collected specimens that were included in the clinical study.

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complexity simplified.

Table 17 - Demographic Information for Pre-Selected Clinical Specimens
	# Samples (%)
Gender
Male	24(38.1%)
Female	25(39.7%)
Gender Unknown	14(22.2%)
Total	63(100.0%)
Age (years)
0-1	0(0.0%)
>1-5	1(1.6%)
>5-21	0(0.0%)
>21-65	27(42.9%)
>65	19(30.2%)
Age Unknown	16(25.4%)
Total	63(100.0%)
Subject Status
Hospitalized	2(3.2%)
Status Unknown	61(96.8%)
Total	63(100.0%)
Blood Culture Bottle Type
BD BACTEC Lytic Anaerobic	2(3.2%)
BD BACTEC Plus Aerobic	17(27.0%)
BD BACTEC Standard Aerobic	29(46.0%)
Bottle Type Unknown	15(23.8%)
Total	63(100.0%)

A total of 829 specimens were contrived and tested. To minimize bias, contrived specimens were blinded, randomized, and tested along with negative clinical specimens at all four testing sites during June 2023. Results from contrived specimens were analyzed separately from the prospective and pre-selected data sets.

Out of the 829 specimens included in the contrived study analysis, 803 specimens (96.9%) generated valid BCY Assay results (i.e., Detected or Not Detected) on the first attempt. There were 26 specimens (3.1%) with an invalid result on the initial run. Of the 26 specimens retested, 24 specimens generated a valid result after a single retest for a final success rate of 99.7% (827/829).

The invalid rate for prospective, pre-selected, and contrived specimens combined was 2.9% (28/961) after the initial run. After allowing for a single retest of any initial invalid results, 26 (2.7%) specimens generated valid BCY results. Two (0.2%) specimens remained invalid on repeat for an overall success rate of 99.8% (959/961).

For each target in the BCY Assay Panel, the diagnostic performance of the BCY Assay was determined using Sensitivity/PPA and Specificity/NPA, along with the associated 95% confidence intervals, (95% Cl as compared to the reference method). The results of the combined prospective and pre-selected specimen analysis are summarized in Table 18. The performance of the BCY Assay for contrived specimens is presented separately in Table 19.

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		Sensitivity / PPA1			Specificity / NPA2
Pathogen Target		TP /(TP+FN)	Sensitivity/ PPA1	95% CI	TN /(TN+FP)	Specificity/ NPA2	95% CI
	Prospective	17/17	100.0%	81.6%-100.0%	51/52	98.1%	89.9%-99.7%
Candida albicans	Pre-selected	17/17	100.0%	81.6%-100.0%	46/46	100.0%	92.3%-100.0%
	Combined	34/34	100.0%	89.8%-100.0%	97/98	99.0%	94.4%-99.8%
	Prospective	4/4	100.0%	51.0%-100.0%	65/65	100.0%	94.4%-100.0%
Candida auris	Pre-selected	0/0	NA	NA	63/63	100.0%	94.3%-100.0%
	Combined	4/4	100.0%	51.0%-100.0%	128/128	100.0%	97.1%-100.0%
	Prospective	0/0	NA	NA	69/69	100.0%	94.7%-100.0%
Candidadubliniensis	Pre-selected	0/0	NA	NA	63/63	100.0%	94.3%-100.0%
	Combined	0/0	NA	NA	132/132	100.0%	97.2%-100.0%
	Prospective	0/0	NA	NA	69/69	100.0%	94.7%-100.0%
Candida famata	Pre-selected	0/0	NA	NA	63/63	100.0%	94.3%-100.0%
	Combined	0/0	NA	NA	132/132	100.0%	97.2%-100.0%
	Prospective	25/25	100.0%	86.7%-100.0%	44/44	100.0%	92.0%-100.0%
Candida glabrata	Pre-selected	21/21	100.0%	84.5%-100.0%	42/42	100.0%	91.6%-100.0%
	Combined	46/46	100.0%	92.3%-100.0%	86/86	100.0%	95.7%-100.0%
	Prospective	0/0	NA	NA	69/69	100.0%	94.7%-100.0%
Candidaguilliermondii	Pre-selected	0/0	NA	NA	63/63	100.0%	94.3%-100.0%
	Combined	0/0	NA	NA	132/132	100.0%	97.2%-100.0%
Candidahaemulonii/C.duobushaemulonii	Prospective	0/0	NA	NA	69/69	100.0%	94.7%-100.0%
	Pre-selected	0/0	NA	NA	63/63	100.0%	94.3%-100.0%
	Combined	0/0	NA	NA	132/132	100.0%	97.2%-100.0%
	Prospective	1/1	100.0%	20.7%-100.0%	68/68	100.0%	94.7%-100.0%
Candida kefyr	Pre-selected	0/0	NA	NA	63/63	100.0%	94.3%-100.0%
LIAISON PLEX® Yeast Blood Culture Assay Traditional 510(k) Submission
			Sensitivity / PPA1		Specificity / NPA2
Pathogen Target		TP /(TP+FN)	Sensitivity/ PPA1	95% CI	TN /(TN+FP)	Specificity/ NPA2	95% CI
	Combined	1/1	100.0%	20.7%-100.0%	131/131	100.0%	97.2%-100.0%
	Prospective	3/3	100.0%	43.9%-100.0%	66/66	100.0%	94.5%-100.0%
Candida krusei	Pre-selected	1/1	100.0%	20.7%-100.0%	62/62	100.0%	94.2%-100.0%
	Combined	4/4	100.0%	51.0%-100.0%	128/128	100.0%	97.1%-100.0%
	Prospective	0/0	NA	NA	69/69	100.0%	94.7%-100.0%
Candida lipolytica	Pre-selected	0/0	NA	NA	63/63	100.0%	94.3%-100.0%
	Combined	0/0	NA	NA	132/132	100.0%	97.2%-100.0%
Candidalusitaniae	Prospective	2/2	100.0%	34.2%-100.0%	67/67	100.0%	94.6%-100.0%
	Pre-selected	0/0	NA	NA	63/63	100.0%	94.3%-100.0%
	Combined	2/2	100.0%	34.2%-100.0%	130/130	100.0%	97.1%-100.0%
	Prospective	11/11	100.0%	74.1%-100.0%	57/58	98.3%	90.9%-99.7%
Candidaparapsilosis	Pre-selected	6/6	100.0%	61.0%-100.0%	57/57	100.0%	93.7%-100.0%
	Combined	17/17	100.0%	81.6%-100.0%	114/1154	99.1%	95.2%-99.8%
Candidatropicalis	Prospective	6/6	100.0%	61.0%-100.0%	60/63	95.2%	86.9%-98.4%
	Pre-selected	0/0	NA	NA	63/63	100.0%	94.3%-100.0%
	Combined	6/6	100.0%	61.0%-100.0%	123/1265	97.6%	93.2%-99.2%
	Prospective	0/0	NA	NA	69/69	100.0%	94.7%-100.0%
Cryptococcusneoformans/Cryptococcus gattii	Pre-selected	5/5	100.0%	56.6%-100.0%	58/58	100.0%	93.8%-100.0%
	Combined	5/5	100.0%	56.6%-100.0%	127/127	100.0%	97.1%-100.0%

Table 18. LIAISON PLEX BCY Assay Performance with Prospective and Pre-Selected Specimens

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1 Sensitivity is designated for prospective sample testing, while PPA is designated for pre-selected sample testing. 2 Specificity is designated for prospective sample testing, while NPA is designated for pre-selected sample testing.

3The one Candida albicans False Positive was positive by a cleared molecular assay.

4The one Candida parapsilosis False Positive was positive by a cleared molecular assay.

5One out of three Candida tropicalis False Positive by a cleared molecular assay.

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LIAISON PLEX® Yeast Blood Culture Assay Traditional 510(k) Submission Table 19 – LIAISON PLEX BCY Assay Performance with Contrived Specimens

Pathogen Target	Positive Percent Agreement			Negative Percent Agreement
Analyte	TP / (TP+FN)	PPA	95% CI	TN / (TN+FP)	NPA	95% CI
Candida albicans	50/50	100.0%	92.9%- 100.0%	777/777	100.0%	99.5%- 100.0%
Candida auris	50/50	100.0%	92.9%- 100.0%	777/777	100.0%	99.5%- 100.0%
Candida dubliniensis	50/50	100.0%	92.9%- 100.0%	777/777	100.0%	99.5%- 100.0%
Candida famata	50/50	100.0%	92.9%- 100.0%	776/7771	99.9%	99.3%- 100.0%
Candida glabrata	49/49	100.0%	92.7%- 100.0%	778/778	100.0%	99.5%- 100.0%
Candida guilliermondii	50/50	100.0%	92.9%- 100.0%	777/777	100.0%	99.5%- 100.0%
Candida haemulonii/C. duobushaemulonii	50/50	100.0%	92.9%- 100.0%	777/777	100.0%	99.5%- 100.0%
Candida kefyr	50/50	100.0%	92.9%- 100.0%	777/777	100.0%	99.5%- 100.0%
Candida krusei	50/50	100.0%	92.9%- 100.0%	777/777	100.0%	99.5%- 100.0%
Candida lipolytica	50/50	100.0%	92.9%- 100.0%	777/777	100.0%	99.5%- 100.0%
Candida lusitaniae	50/50	100.0%	92.9%- 100.0%	777/777	100.0%	99.5%- 100.0%
Candida parapsilosis	50/50	100.0%	92.9%- 100.0%	776/7772	99.9%	99.3%- 99.9%
Candida tropicalis	49/49	100.0%	92.7%- 100.0%	775/7783	99.6%	98.9%- 100.0%
Cryptococcus neoformans/Cryptococcus gattii	100/100	100.0%	96.3%- 100.0%	727/727	100.0%	99.5%- 100.0%

The clinical performance of the LIAISON PLEX® BCY Assay was compared to the standard of care culture followed by identification by Matrix Assisted Laser Desorption/lonization coupled to time-of-flight Mass Spectrometry (MALDI-TOF MS) for all targets, as summarized below in Table 20.

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LIAISON PLEX® Yeast Blood Culture Assay Traditional 510(k) Submission

LIAISON PLEX® BCY Assay Target	Comparator Method
Candida albicans	Standard of Care culture followed byidentification by MALDI-TOF MS
Candida auris
Candida dubliniensis
Candida famata
Candida glabrata
Candida guilliermondii
Candida kefyr
Candida krusei
Candida lipolytica
Candida lusitaniae
Candida parapsilosis
Candida tropicalis
Candida haemulonii/duobushaemulonii (1)
Cryptococcus neoformans / gattii

Table 20 - Reference Method for the LIAISON PLEX BCY Assay Clinical Study

The pre-defined acceptance criteria for the clinical study were defined as follows:

The assay shall achieve a target Sensitivity of ≥ 90% for all targets. .
The Specificity for each target should be established at a level of ≥95%. .
Failure rate shall be ≤15%. .

Acceptance Criteria are based on Arms 1, 2, and 3 combined. All acceptance criteria were met successfully.

The study results demonstrate that the diagnostic accuracy of the BCY Assay is acceptable for the safe and effective detection and identification of fungal pathogens from blood culture media identified as positive by a continuous monitoring blood culture system and which contain fungal organisms as determined by Gram Stain from patients exhibiting clinical signs and symptoms of bloodstream infection.

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M. Proposed Labeling:

The labeling provided in the submission satisfies the requirements of 21 CFR 809.10.

N. Conclusion:

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

Regulation Number and Section

§ 866.3365 Multiplex nucleic acid assay for identification of microorganisms and resistance markers from positive blood cultures.

(a)
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.(b)
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).