LIAISON PLEX Gram-Positive Blood Culture Assay

K243490 · Luminex Corporation · PAM · Jun 6, 2025 · Microbiology

Device Facts

Record IDK243490
Device NameLIAISON PLEX Gram-Positive Blood Culture Assay
ApplicantLuminex Corporation
Product CodePAM · Microbiology
Decision DateJun 6, 2025
DecisionSESE
Submission TypeTraditional
Regulation21 CFR 866.3365
Device ClassClass 2

Intended Use

The LIAISON PLEX® Gram-Positive Blood Culture (BCP) Assay, performed using the automated, sample-to-result LIAISON PLEX® System, is a qualitative multiplexed in vitro diagnostic test for the simultaneous detection and identification of selected gram-positive pathogens and/or selected genetic determinants associated with antimicrobial resistance in positive blood culture bottles. The LIAISON PLEX BCP Assay is performed directly on blood culture media using blood culture bottles identified as positive by a continuous monitoring blood culture system and which contain gram-positive bacteria as determined by Gram stain. The LIAISON PLEX® BCP Assay contains targets for the detection of genetic determinants associated with resistance to methicillin (mecA/mecC) and vancomycin (vanA and vanB) to aid in the identification of potentially antimicrobial-resistant organisms in positive blood culture samples. In mixed growth, the LIAISON PLEX BCP Assay does not specifically attribute vanA/vanB-mediated vancomycin resistance to either E. faecalis or E. faecium, or mecA/mecC-mediated methicillin resistance to either Staphylococcus spp., S. aureus, S. epidermidis or S. lugdunensis. The antimicrobial resistance gene or marker detected may or may not be associated with the agent responsible for disease. Negative results for these select antimicrobial resistance gene and marker assays do not indicate susceptibility, as multiple mechanisms of methicillin and vancomycin resistance exist. The LIAISON PLEX® BCP Assay is indicated for use in conjunction with other clinical and laboratory findings to aid in the diagnosis of bacterial bloodstream infections (BSI). The LIAISON PLEX® BCP Assay is not intended to monitor these infections. Sub-culturing of positive blood cultures is necessary to recover organisms for antimicrobial susceptibility testing (AST), for identification of organisms not detected by the LIAISON PLEX BCP Assay, to detect mixed infections that may not be detected by the LIAISON PLEX BCP Assay, for association of antimicrobial resistance genes to a specific organism, or for epidemiological typing.

Device Story

Automated, sample-to-answer, bench-top diagnostic system; processes positive blood culture bottles containing gram-positive bacteria. Workflow: user loads sample into disposable cartridge; system performs mechanical/chemical cell lysis and magnetic bead-based nucleic acid isolation; no PCR amplification. Extracted nucleic acids hybridize to target-specific capture DNA on a microarray; gold nanoparticle probes bind to targets; silver enhancement enables light-scatter measurement. Output: qualitative detection/identification of gram-positive pathogens and resistance markers. Used in clinical laboratories by trained personnel. Results aid clinicians in diagnosing bacterial bloodstream infections; sub-culturing remains necessary for AST and epidemiological typing.

Clinical Evidence

Multi-site clinical study (4 US sites) evaluated 562 prospective specimens, supplemented by 162 pre-selected and 225 contrived specimens. Comparator: culture followed by VITEK 2 or PCR/BDS. Overall testing success rate 99.9%. Sensitivity/PPA and specificity/NPA were high across targets (e.g., S. aureus sensitivity 99.4%, specificity 99.8%; Enterococcus faecalis sensitivity 100%, specificity 100%).

Technological Characteristics

Automated bench-top system; disposable test cartridge. Nucleic acid extraction via mechanical/chemical lysis and magnetic beads. Detection via microarray-based hybridization with gold nanoparticle probes and silver enhancement. Non-amplified (no PCR). Connectivity: barcode scanning for sample/cartridge ID. Standards: ISO 14971, IEC 62366-1, ISO 62304, IEC 61010-1, IEC 60601-1-2.

Indications for Use

Indicated for use in conjunction with other clinical and laboratory findings to aid in the diagnosis of bacterial bloodstream infections (BSI) in patients with positive blood culture bottles containing gram-positive bacteria. Detects Bacillus spp., Enterococcus faecalis, Enterococcus faecium, Listeria spp., Staphylococcus spp., S. aureus, S. epidermidis, S. lugdunensis, Streptococcus spp., S. agalactiae, S. anginosus group, S. pneumoniae, S. pyogenes, and resistance markers mecA/mecC, vanA, and vanB. Not intended to monitor treatment.

Regulatory Classification

Identification

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

Special Controls

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

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

Predicate Devices

Related Devices

Submission Summary (Full Text)

{0} FDA U.S. FOOD & DRUG ADMINISTRATION June 6, 2025 Luminex Corporation Rocio Rueda Senior Regulatory Affairs Associate 4088 Commercial Avenue Northbrook, Illinois 60062 Re: K243490 Trade/Device Name: LIAISON PLEX Gram-Positive 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: PAM Dated: November 7, 2024 Received: November 12, 2024 Dear Rocio Rueda: We have reviewed your section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food, Drug, and Cosmetic Act (the Act) that do not require approval of a premarket approval application (PMA). You may, therefore, market the device, subject to the general controls provisions of the Act. Although this letter refers to your product as a device, please be aware that some cleared products may instead be combination products. The 510(k) Premarket Notification Database available at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/pmn.cfm identifies combination product submissions. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading. If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. In addition, FDA may publish further announcements concerning your device in the Federal Register. U.S. Food & Drug Administration 10903 New Hampshire Avenue Silver Spring, MD 20993 www.fda.gov {1} K243490 - Rocio Rueda Page 2 Additional information about changes that may require a new premarket notification are provided in the FDA guidance documents entitled "Deciding When to Submit a 510(k) for a Change to an Existing Device" (https://www.fda.gov/media/99812/download) and "Deciding When to Submit a 510(k) for a Software Change to an Existing Device" (https://www.fda.gov/media/99785/download). Your device is also subject to, among other requirements, the Quality System (QS) regulation (21 CFR Part 820), which includes, but is not limited to, 21 CFR 820.30, Design controls; 21 CFR 820.90, Nonconforming product; and 21 CFR 820.100, Corrective and preventive action. Please note that regardless of whether a change requires premarket review, the QS regulation requires device manufacturers to review and approve changes to device design and production (21 CFR 820.30 and 21 CFR 820.70) and document changes and approvals in the device master record (21 CFR 820.181). Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Part 801 and Part 809); medical device reporting (reporting of medical device-related adverse events) (21 CFR Part 803) for devices or postmarketing safety reporting (21 CFR Part 4, Subpart B) for combination products (see https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safety-reporting-combination-products); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820) for devices or current good manufacturing practices (21 CFR Part 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR Parts 1000-1050. All medical devices, including Class I and unclassified devices and combination product device constituent parts are required to be in compliance with the final Unique Device Identification System rule ("UDI Rule"). The UDI Rule requires, among other things, that a device bear a unique device identifier (UDI) on its label and package (21 CFR 801.20(a)) unless an exception or alternative applies (21 CFR 801.20(b)) and that the dates on the device label be formatted in accordance with 21 CFR 801.18. The UDI Rule (21 CFR 830.300(a) and 830.320(b)) also requires that certain information be submitted to the Global Unique Device Identification Database (GUDID) (21 CFR Part 830 Subpart E). For additional information on these requirements, please see the UDI System webpage at https://www.fda.gov/medical-devices/device-advice-comprehensive-regulatory-assistance/unique-device-identification-system-udi-system. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to https://www.fda.gov/medical-devices/medical-device-safety/medical-device-reporting-mdr-how-report-medical-device-problems. For comprehensive regulatory information about medical devices and radiation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/medical-devices/device-advice-comprehensive-regulatory-assistance) and CDRH Learn (https://www.fda.gov/training-and-continuing-education/cdrh-learn). Additionally, you may contact the Division of Industry and Consumer Education (DICE) to ask a question about a specific regulatory topic. See the DICE website (https://www.fda.gov/medical-devices/device-advice-comprehensive-regulatory- {2} K243490 - Rocio Rueda Page 3 assistance/contact-us-division-industry-and-consumer-education-dice) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100). Sincerely, Noel J. Gerald -S Noel J. Gerald, Ph.D. Deputy Division Director Division of Microbiology Devices OHT7: Office of In Vitro Diagnostics Office of Product Evaluation and Quality Center for Devices and Radiological Health Enclosure {3} DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration Indications for Use Form Approved: OMB No. 0910-0120 Expiration Date: 07/31/2026 See PRA Statement below. 510(k) Number (if known) K243490 Device Name LIAISON PLEX® Gram-Positive Blood Culture Assay Indications for Use (Describe) The LIAISON PLEX® Gram-Positive Blood Culture Assay (BCP), performed using the automated, sample-to-result LIAISON PLEX® System, is a qualitative multiplexed in vitro diagnostic test for the simultaneous detection and identification of selected gram-positive pathogens and/or selected genetic determinants associated with antimicrobial resistance in positive blood culture bottles. BCP is performed directly on blood culture media using blood culture bottles identified as positive by a continuous monitoring blood culture system and which contain gram-positive bacteria as determined by Gram stain. The BCP Assay detects and identifies the following: Gram Positive Resistance Markers(a): mecA/mecC vanA vanB Genera and Species: Bacillus spp. Enterococcus faecalis Enterococcus faecium Listeria spp. Staphylococcus spp. Staphylococcus aureus Staphylococcus epidermidis Staphylococcus lugdunensis Streptococcus spp. Streptococcus agalactiae Streptococcus anginosus group Streptococcus pneumoniae Streptococcus pyogenes (a) Negative results for antimicrobial resistance genes do not indicate bacterial susceptibility as there are multiple mechanisms that can contribute to resistance. The LIAISON PLEX® BCP Assay contains targets for the detection of genetic determinants associated with resistance to methicillin (mecA/C) and vancomycin (vanA and vanB) to aid in the identification of potentially antimicrobial-resistant organisms in positive blood culture samples. In mixed growth, the LIAISON PLEX BCP Assay does not specifically attribute vanA/vanB-mediated vancomycin resistance to either E. faecalis or E. faecium, or mecA/mecC-mediated methicillin resistance to either Staphylococcus spp., S. aureus, S. epidermidis or S. lugdunensis. The antimicrobial resistance gene or marker detected may or may not be associated with the agent responsible for disease. Negative results for these select antimicrobial resistance gene and marker assays do not indicate susceptibility, as multiple mechanisms of methicillin and vancomycin resistance exist. The LIAISON PLEX® BCP Assay is indicated for use in conjunction with other clinical and laboratory findings to aid in the diagnosis of bacterial bloodstream infections (BSI). The LIAISON PLEX® BCP Assay is not intended to monitor FORM FDA 3881 (8/23) Page 1 of 2 PSC Publishing Services (301) 443-6740 {4} these infections. Sub-culturing of positive blood cultures is necessary to recover organisms for antimicrobial susceptibility testing (AST), for identification of organisms not detected by the LIAISON PLEX BCP Assay, to detect mixed infections that may not be detected by the LIAISON PLEX BCP Assay, for association of antimicrobial resistance genes to a specific organism, or for epidemiological typing. Type of Use (Select one or both, as applicable) ☑ Prescription Use (Part 21 CFR 801 Subpart D) ☐ Over-The-Counter Use (21 CFR 801 Subpart C) # CONTINUE ON A SEPARATE PAGE IF NEEDED. This section applies only to requirements of the Paperwork Reduction Act of 1995. # *DO NOT SEND YOUR COMPLETED FORM TO THE PRA STAFF EMAIL ADDRESS BELOW.* The burden time for this collection of information is estimated to average 79 hours per response, including the time to review instructions, search existing data sources, gather and maintain the data needed and complete and review the collection of information. Send comments regarding this burden estimate or any other aspect of this information collection, including suggestions for reducing this burden, to: Department of Health and Human Services Food and Drug Administration Office of Chief Information Officer Paperwork Reduction Act (PRA) Staff PRAStaff@fda.hhs.gov "An agency may not conduct or sponsor, and a person is not required to respond to, a collection of information unless it displays a currently valid OMB number." FORM FDA 3881 (8/23) Page 2 of 2 PSC Publishing Services (301) 443-6740 {5} Diasorin LIAISON PLEX® Gram-Positive Blood Culture Assay Traditional 510(k) # 510(k) Summary This Summary of 510(k) safety and effectiveness information is being submitted in accordance with the requirements of 21 CFR 807.92. Preparation date: 04 April 2025 A. 510(k) Number: K243490 B. Purpose for Submission: Traditional 510(k), New Device C. Measurand: Nucleic acid sequences for the following organisms: Bacillus spp., Enterococcus faecalis, Enterococcus faecium, Listeria spp., Staphylococcus spp., Staphylococcus aureus, Staphylococcus epidermidis, Staphylococcus lugdunensis, Streptococcus spp., Streptococcus agalactiae, Streptococcus anginosus group, Streptococcus pneumoniae, Streptococcus pyogenes Nucleic acid sequences for the following resistance markers: mecA/mecC, vanA, vanB D. Type of Test: Qualitative Multiplexed Direct Detection Hybridization Assay E. Applicant: Rocio Rueda, Luminex Corporation 4088 Commercial Avenue Northbrook, IL 60062 (847) 400-9000 F. Proprietary and Established Names: LIAISON PLEX® Gram-Positive Blood Culture Assay G. Regulatory Information: | Product Code | Classification | Regulation Section | Panel | | --- | --- | --- | --- | | PAM | II | 21 CFR 866.3365 – Multiplex Nucleic Acid Assay for Identification of Microorganisms and Resistance Markers from Positive Blood Cultures | 83 (Microbiology) | Confidential & Restricted 510(k) Summary {6} Diasorin LIAISON PLEX® Gram-Positive Blood Culture Assay Traditional 510(k) ## H. Intended Use: ### 1. Intended use(s): The LIAISON PLEX® Gram-Positive Blood Culture (BCP) Assay, performed using the automated, sample-to-result LIAISON PLEX® System, is a qualitative multiplexed in vitro diagnostic test for the simultaneous detection and identification of selected gram-positive pathogens and/or selected genetic determinants associated with antimicrobial resistance in positive blood culture bottles. The LIAISON PLEX BCP Assay is performed directly on blood culture media using blood culture bottles identified as positive by a continuous monitoring blood culture system and which contain gram-positive bacteria as determined by Gram stain. The LIAISON PLEX BCP Assay detects and identifies the following: | Gram-Positive Resistance Markers^{a} | Genera and Species | | --- | --- | | mecA/mecC | Bacillus spp. | | vanA | Enterococcus faecalis | | vanB | Enterococcus faecium | | | Listeria spp. | | | Staphylococcus spp. | | | Staphylococcus aureus | | | Staphylococcus epidermidis | | | Staphylococcus lugdunensis | | | Streptococcus spp. | | | Streptococcus agalactiae | | | Streptococcus anginosus group | | | Streptococcus pneumoniae | | | Streptococcus pyogenes | a Negative results for antimicrobial resistance genes do not indicate bacterial susceptibility as there are multiple mechanisms that can contribute to resistance. The LIAISON PLEX® BCP contains targets for the detection of genetic determinants associated with resistance to methicillin (mecA/mecC) and vancomycin (vanA and vanB) to aid in the identification of potentially antimicrobial-resistant organisms in positive blood culture samples. In mixed growth, the LIAISON PLEX® BCP Assay does not specifically attribute vanA/vanB-mediated vancomycin resistance to either E. faecalis or E. faecium, or mecA/mecC-mediated methicillin resistance to either Staphylococcus spp., S. aureus, S. epidermidis or S. lugdunensis. The antimicrobial resistance gene or marker detected may or may not be associated with the agent Confidential & Restricted 510(k) Summary {7} Diasorin LIAISON PLEX® Gram-Positive Blood Culture Assay Traditional 510(k) responsible for disease. Negative results for these select antimicrobial resistance gene and marker assays do not indicate susceptibility, as multiple mechanisms of methicillin and vancomycin resistance exist. The LIAISON PLEX BCP Assay is indicated for use in conjunction with other clinical and laboratory findings to aid in the diagnosis of bacterial bloodstream infections (BSI). The LIAISON PLEX BCP Assay is not intended to monitor treatment of these infections. Sub-culturing of positive blood cultures is necessary to recover organisms for antimicrobial susceptibility testing (AST), for identification of organisms not detected by LIAISON PLEX BCP Assay, to detect mixed infections that may not be detected by the LIAISON PLEX BCP Assay, for association of antimicrobial resistance genes to a specific organism, or for epidemiological typing. Confidential & Restricted 510(k) Summary Page 3 of 43 {8} Diasorin LIAISON PLEX® Gram-Positive Blood Culture Assay Traditional 510(k) 2. Indication(s) for use: Same as intended use. 3. Special conditions for use statement(s): For prescription use only. For in vitro diagnostic use only. 4. Special instrument requirements: For use with LIAISON PLEX® Systems. # I. Device Description: The LIAISON PLEX® Gram-Positive Blood Culture Assay (BCP Assay) is an automated test for the detection and identification of nucleic acid from gram-positive bacteria in a positive blood culture media sample. The BCP Assay is performed directly on blood culture media using blood culture bottles identified as positive by a continuous monitoring blood culture system, and which contain gram-positive bacteria, as determined by a Gram stain. The LIAISON PLEX® System is a fully automated, bench-top "sample-to-answer" device that performs sample preparation and microarray-based hybridization for the detection of target-specific nucleic acids. The test reagents are supplied as a single, disposable test cartridge. Target amplification is not performed as part of the BCP Assay workflow, as it is a non-amplified, direct detection test performed on the LIAISON PLEX® System. # J. Substantial Equivalence Information: 1. Predicate device name(s): VERIGENE Blood Culture Gram-Positive (BC-GP) Nucleic Acid Test 2. Predicate 510(k) number(s): K122514 3. Comparison with predicate: The following tables compare the LIAISON PLEX® Gram-Positive Blood Culture Assay to the VERIGENE Blood Culture Gram-Positive (BC-GP) Nucleic Acid Test. | Comparison to Predicate Device | Predicate Device: VERIGENE Blood Culture Gram-Positive (BC-GP) Nucleic Acid Test, K122514 | Candidate Device: LIAISON PLEX® Gram-Positive Blood Culture Assay | | --- | --- | --- | | Product Code | PAM | PAM | | Regulation Number | 21 CFR 866.3365 | 21 CFR 866.3365 | Confidential & Restricted 510(k) Summary {9} Diasorin LIAISON PLEX® Gram-Positive Blood Culture Assay Traditional 510(k) | Comparison to Predicate Device | Predicate Device: VERIGENE Blood Culture Gram-Positive (BC-GP) Nucleic Acid Test, K122514 | Candidate Device: LIAISON PLEX® Gram-Positive Blood Culture Assay | | --- | --- | --- | | Organism Detected | Organisms: Staphylococcus spp., Staphylococcus aureus, Staphylococcus epidermidis, Staphylococcus lugdunensis, Streptococcus spp., Streptococcus pneumoniae, Streptococcus pyogenes, Streptococcus agalactiae, Streptococcus anginosus group, Enterococcus faecalis, Enterococcus faecium, Listeria spp. Resistance Markers: mecA, vanA, vanB | Organisms: Bacillus spp., Enterococcus faecalis, Enterococcus faecium, Listeria spp., Staphylococcus spp., Staphylococcus aureus, Staphylococcus epidermidis, Staphylococcus lugdunensis, Streptococcus spp., Streptococcus agalactiae, Streptococcus anginosus group, Streptococcus pneumoniae, Streptococcus pyogenes Resistant markers: mecA/mecC, vanA, vanB | | Measurand | Nucleic acid from Organisms detected | Same | | Intended Use | The Verigene® Gram-Positive Blood Culture Nucleic Acid Test (BC-GP), performed using the sample-to-result Verigene System, is a qualitative multiplexed in vitro diagnostic test for the simultaneous detection and identification of potentially pathogenic gram-positive bacteria which may cause bloodstream infection (BSI). BC-GP is performed directly on blood culture bottles identified as positive by a continuous monitoring blood culture system and which contain gram-positive bacteria. BC-GP detects and identifies the following: Bacterial Genera and Species Staphylococcus spp. Staphylococcus aureus Staphylococcus epidermidis Staphylococcus lugdunensis Streptococcus spp. Streptococcus pneumoniae Streptococcus pyogenes Streptococcus agalactiae Streptococcus anginosus group Enterococcus faecalis Enterococcus faecium Listeria spp. | The LIAISON PLEX® Gram-Positive Blood Culture Assay (BCP), performed using the automated, sample-to-result LIAISON PLEX® System, is a qualitative multiplexed in vitro diagnostic test for the simultaneous detection and identification of selected gram-positive pathogens and/or selected genetic determinants associated with antimicrobial resistance in positive blood culture bottles. BCP is performed directly on blood culture media using blood culture bottles identified as positive by a continuous monitoring blood culture system and which contain gram-positive bacteria as determined by Gram stain. The BCP Assay detects and identifies the following: Genera and Species Bacillus spp. Enterococcus faecalis Enterococcus faecium Listeria spp. Staphylococcus spp. Staphylococcus aureus Staphylococcus epidermidis Staphylococcus lugdunensis Streptococcus spp. Streptococcus agalactiae Streptococcus anginosus group Streptococcus pneumoniae Streptococcus pyogenes | | | Resistance Markers¹ mecA vanA vanB | | | | ¹In mixed growth, BC-GP | | Confidential & Restricted 510(k) Summary {10} Diasorin LIAISON PLEX® Gram-Positive Blood Culture Assay Traditional 510(k) | Comparison to Predicate Device | Predicate Device: VERIGENE Blood Culture Gram-Positive (BC-GP) Nucleic Acid Test, K122514 | Candidate Device: LIAISON PLEX® Gram-Positive Blood Culture Assay | | --- | --- | --- | | | does not specifically attribute van-mediated vancomycin resistance to either E. faecalis or E. faecium, or mecA-mediated methicillin resistance to either S. aureus or S. epidermidis. BC-GP is indicated for use in conjunction with other clinical and laboratory findings to aid in the diagnosis of bacterial bloodstream infections; however, it is not used to monitor these infections. Sub-culturing of positive blood cultures is necessary to recover organisms for antimicrobial susceptibility testing (AST), for identification of organisms not detected by BC-GP, differentiation of mixed growth, for association of antimicrobial resistance marker genes to a specific organism, or for epidemiological typing. | **Resistance Markers*** mecA/mecC vanA vanB | | | | *Negative results for antimicrobial resistance genes do not indicate bacterial susceptibility as there are multiple mechanisms that can contribute to resistance. The LIAISON PLEX BCP Assay contains targets for the detection of genetic determinants associated with resistance to methicillin (mecA/mecC) and vancomycin (vanA and vanB) to aid in the identification of potentially antimicrobial-resistant organisms in positive blood culture samples. In mixed growth, BCP does not specifically attribute vanA/vanB-mediated vancomycin resistance to either E. faecalis or E. faecium, or mecA/mecC-mediated methicillin resistance to either Staphylococcus spp., S. aureus, S. epidermidis or S. lugdunensis. The antimicrobial resistance gene or marker detected may or may not be associated with the agent responsible for disease. Negative results for these select antimicrobial resistance gene and marker assays do not indicate susceptibility, as multiple mechanisms of methicillin and vancomycin resistance exist. The LIAISON PLEX® BCP Assay is indicated for use in conjunction with other clinical and laboratory findings to aid in the diagnosis of bacterial bloodstream infections (BSI). The LIAISON PLEX® BCP Assay is not intended to monitor these infections. Sub-culturing of positive blood cultures is necessary to recover organisms for antimicrobial susceptibility testing (AST), for identification of organisms not detected by LIAISON PLEX BCP Assay, to detect mixed infections that may not be detected by the LIAISON PLEX BCP Assay, for association of antimicrobial resistance genes to a specific organism, or for epidemiological typing. | Confidential & Restricted 510(k) Summary Page 6 of 43 {11} Diasorin LIAISON PLEX® Gram-Positive Blood Culture Assay Traditional 510(k) | Automated System (Sample to Answer) | Automated | Same | | --- | --- | --- | | Instrumentation | VERIGENE | LIAISON PLEX® | | Sample Types | Positive Blood Culture | Same | Confidential & Restricted 510(k) Summary Page 7 of 43 {12} Diasorin LIAISON PLEX® Gram-Positive Blood Culture Assay Traditional 510(k) # K. Standards/Guidance Documents Referenced: - Class II Special Controls Guideline: Multiplex Nucleic Acid Assay for Identification of Microorganisms and Resistance Markers from Positive Blood Cultures (May 2015) - Electronic Submission Template for Medical Device 510(k) Submissions - Guidance for Industry and Food and Drug Administration Staff (October 2, 2023). - Content of Premarket Submissions for Device Software Functions - Guidance for Industry and Food and Drug Administration Staff (June 14, 2023). - Cybersecurity in Medical Devices: Quality System Considerations and Content of Premarket Submissions - Guidance for Industry and Food and Drug Administration Staff (September 23, 2023). - Statistical Guidance on Reporting Results from Studies Evaluating Diagnostic Tests - Guidance for Industry and FDA Staff (March 13, 2007). - CLSI. User Protocol for Evaluation of Qualitative Test Performance; Approved Guideline - Second Edition. CLSI document EP12-A2. Wayne, PA: Clinical and Laboratory Standards Institute; 2008. - CLSI. Evaluation of Stability of In Vitro Diagnostic Reagents; Approved Guideline. CLSI document EP25-A. Wayne, PA: Clinical and Laboratory Standards Institute; 2009. - ISO 14971:2019 Medical devices - Application of risk management to medical devices - IEC 62366-1:2015 +A1:2020 Medical devices - Part 1: Application of usability engineering to medical devices - ISO 62304:2006 Medical device software - Software life-cycle processes - ISO 15223-1:2021: Medical Devices - Symbols to be used with medical device labels, labeling and information to be supplied - Part 1: General requirements - IEC 61010-1 Ed. 3.1 2017-01: Safety requirements for electrical equipment for measurement, control, and laboratory use - Part 1: General requirements - EN 61010-2-101:2002/IEC 61010-2-101:2015: Safety requirements for electrical equipment for measurement, control and laboratory use - Part 2-101: Particular requirements for in vitro diagnostic (IVD) medical equipment. - IEC 60601-1-2:2014 (Edition 4.0): Medical electrical equipment - Part 1-2: General requirements for basic safety and essential performance - Collateral Standard: Electromagnetic disturbances - Requirements and tests - ISO 13485:2016/EN ISO 13485:2016; Medical devices - Quality Management System - Requirements for regulatory purposes - ISO 20916:2019; In vitro diagnostic medical devices. Clinical performance studies using specimens from human subjects. Good study practice - EN ISO 18113-1:2011; In vitro diagnostic medical devices - Information supplied by the manufacturer (labeling). Terms, definition and general requirements Confidential & Restricted 510(k) Summary {13} Diasorin LIAISON PLEX® Gram-Positive Blood Culture Assay Traditional 510(k) - 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® Gram-Positive Blood Culture Assay (BCP Assay) is performed directly on blood culture media using blood culture bottles identified as positive by a continuous monitoring blood culture system, and which contain gram-positive bacteria, as determined by a Gram stain. The system consists of an instrument and a single-use, disposable test cartridge. The user loads an aliquot of the sample into the sample port of the LIAISON PLEX® Gram-Positive 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 BCP 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; PCR amplification is not used in this assay. By performing direct detection, the assay specifically detects the viable bacteria and minimizes interference from trace nucleic acids or non-viable bacteria that may be present at much lower levels and potentially lead to false positive results. b) Hybridization: Extracted nucleic acid hybridize to target-specific capture DNA on a microarray format, and target-specific mediator and gold nanoparticle probe hybridize to captured nucleic acids; c) Signal Analysis: Gold nanoparticle probes bound specifically to target-containing spots in the microarray are silver-enhanced, and light scatter from the spots is measured and further analyzed to determine the presence (Detected) or absence (Not Detected) of a target. Confidential & Restricted 510(k) Summary {14} Diasorin LIAISON PLEX® Gram-Positive Blood Culture Assay Traditional 510(k) ## M. Performance Characteristics: ### 1. Analytical performance: #### a. Precision/Reproducibility: **Site-to-site Reproducibility** Site-to-site reproducibility of the LIAISON PLEX® BCP Assay was evaluated by testing LIAISON PLEX® BCP Assay cartridges across five non-consecutive days with at least two operators each at multiple sites; three external sites and one internal site. The reproducibility panel, blinded to operators, consisted of a total of 16 blood culture samples. 7 samples each contained representative on-panel organisms individually cultured at ring positivity, and eight hours after ring positivity, one sample was contrived with an off-panel organism (Escherichia coli), and the last sample was a negative blood culture matrix (NBM) specimen. The blinded reproducibility panel was tested in triplicate by each operator on each testing day for five non-consecutive testing days. The call agreement and 95% confidence intervals are presented in Table 1. Overall, results of site-to-site reproducibility evaluation demonstrated 99.7% reproducibility of the LIAISON PLEX® BCP Assay with a 95% CI of 99.3% to 99.9%. Table 1. LIAISON PLEX® Gram-Positive Blood Culture Assay Site-to-Site Reproducibility Results Summary | Organism ID | Reportable Targets | Sample Type | Agreement (%) with Expected results | | | | 95% CI | | | --- | --- | --- | --- | --- | --- | --- | --- | --- | | | | | Site1 | Site 2 | Site 3 | Overall | Lower | Upper | | Staphylococcus aureus | Staphylococcus spp. S. aureus | Panel 1 – RP | 100% (30/30) | 100% (30/30) | 100% (30/30) | 100% (90/90) | 95.9% | 100% | | | | Panel 1 – RP+8 Hours | 100% (30/30) | 96.7% (29/30)a | 100% (30/30) | 98.9% (89/90) | 94.0% | 99.8% | | Enterococcus faecalis | Enterococcus faecalis | Panel 2 – RP | 100% (30/30) | 100% (30/30) | 100% (30/30) | 100% (90/90) | 95.9% | 100% | | | | Panel 2 – RP+8 Hours | 100% (30/30) | 100% (30/30) | 100% (30/30) | 100% (90/90) | 95.9% | 100% | | Bacillus subtilis | Bacillus spp. | Panel 3 – RP | 100% (30/30) | 100% (30/30) | 100% (30/30) | 100% (90/90) | 95.9% | 100% | | | | Panel 3 – RP+8 Hours | 100% (30/30) | 100% (30/30) | 100% (30/30) | 100% (90/90) | 95.9% | 100% | | Listeria monocytogenes | Listeria spp. | Panel 4 – RP | 100% (30/30) | 100% (30/30) | 96.7% (29/30)c | 98.9% (89/90) | 94.0% | 99.8% | | | | Panel 4 – RP+8 Hours | 100% (30/30) | 100% (30/30) | 100% (30/30) | 100% (90/90) | 95.9% | 100% | | Staphylococcus epidermidis | Staphylococcus spp. Staphylococcus epidermidis | Panel 5 – RP | 100% (30/30) | 100% (30/30) | 100% (30/30) | 100% (90/90) | 95.9% | 100% | | | | Panel 5 – RP+8 Hours | 100% (30/30) | 100% (30/30) | 100% (30/30) | 100% (90/90) | 95.9% | 100% | | Streptococcus pneumoniae | Streptococcus spp. Streptococcus pneumoniae | Panel 6 – RP | 100% (30/30) | 100% (30/30) | 100% (30/30) | 100% (90/90) | 95.9% | 100% | | | | Panel 6 – RP+8 Hours | 100% (30/30) | 100% (30/30) | 100% (30/30) | 100% (90/90) | 95.9% | 100% | | Streptococcus pyogenes | Streptococcus spp. Streptococcus pyogenes | Panel 7 – RP | 100% (30/30) | 100% (30/30) | 96.7% (29/30)d | 98.9% (89/90) | 94.0% | 99.8% | Confidential & Restricted 510(k) Summary {15} Diasorin LIAISON PLEX® Gram-Positive Blood Culture Assay Traditional 510(k) | | | Panel 7 – RP+8 Hours | 100% (30/30) | 100% (30/30) | 100% (30/30) | 100% (90/90) | 95.9% | 100% | | --- | --- | --- | --- | --- | --- | --- | --- | --- | | Escherichia coli | None | Contrived Negative | 100% (60/60) | 100% (60/60) | 100% (60/60) | 100% (180/180) | 97.9% | 100% | | No Target | None | Negative Blood Matrix | 100% (30/30) | 100% (30/30) | 96.7% (29/30)b | 98.9% (89/90) | 94.0% | 99.8% | | Resistance markers | | | | | | | | | | Staphylococcus aureus | mecA/C | Panel 1 – RP | 100% (30/30) | 100% (30/30) | 100% (30/30) | 100% (90/90) | 95.9% | 100% | | | | Panel 1 – RP+8 Hours | 100% (30/30) | 96.7% (29/30) | 100% (30/30) | 98.9% (89/90) | 94.0% | 99.8% | | Enterococcus faecalis | vanB | Panel 2 – RP | 100% (30/30) | 100% (30/30) | 100% (30/30) | 100% (90/90) | 95.9% | 100% | | | | Panel 2 – RP+8 Hours | 100% (30/30) | 100% (30/30) | 100% (30/30) | 100% (90/90) | 95.9% | 100% | | Staphylococcus epidermidis | mecA/mecC | Panel 5 – RP | 100% (30/30) | 100% (30/30) | 100% (30/30) | 100% (90/90) | 95.9% | 100% | | | | Panel 5 – RP+8 Hours | 100% (30/30) | 100% (30/30) | 100% (30/30) | 100% (90/90) | 95.9% | 100% | a False positive S. lugdunensis, S. anginosus group, and Streptococcus spp. result in 1/30 replicates. Reportable targets were fully detected. b False positive E. faecium and vanA result in 1/30 replicates. c False positive S. lugdunensis result in 1/30 replicates. Reportable targets were fully detected. d False positive Staphylococcus spp. result in 1/30 replicates. Reportable targets were fully detected. ## Precision/Repeatability Within laboratory (operator-to-operator) precision/repeatability of the LIAISON PLEX® BCP Assay was evaluated based on the results generated by two operators testing samples (two on-panel organisms (Staphylococcus aureus and Enterococcus faecalis) at ring positivity and at 8 hours after ring positivity, contrived negative and negative blood culture samples) at the internal site (Site 1). Within laboratory precision/repeatability of the LIAISON PLEX® BCP Assay was 100%, and results are summarized in Table 2. Table 2. LIAISON PLEX® Gram-Positive Blood Culture Assay Within-Laboratory Precision/Repeatability Results Summary | Organism ID | Reportable Targets | Sample Type | Agreement (%) | Overall 95% CI | | --- | --- | --- | --- | --- | | Staphylococcus aureus | Staphylococcus spp | S. aureus | Panel 1 – RP | 100% (30/30) | 88.6% - 100% | | Panel 1 – RP+8 Hours | 100% (30/30) | 88.6% - 100% | | Enterococcus faecalis | Enterococcus faecalis | Panel 2 – RP | 100% (30/30) | 88.6% - 100% | | Panel 2 – RP+8 Hours | 100% (30/30) | 88.6% - 100% | | Escherichia coli | None | Contrived Negative | 100% (30/30) | 88.6% - 100% | | No Target | None | Negative Blood Matrix | 100% (30/30) | 88.6% - 100% | | Resistance Markers | | Staphylococcus aureus | mecA/C | Panel 1 – RP | 100% (30/30) | 88.6% - 100% | Confidential & Restricted 510(k) Summary {16} Diasorin LIAISON PLEX® Gram-Positive Blood Culture Assay Traditional 510(k) | | | Panel 1 – RP+8 Hours | 100% (30/30) | 88.6% - 100% | | --- | --- | --- | --- | --- | | Enterococcus faecalis | vanB | Panel 2 – RP | 100% (30/30) | 88.6% - 100% | | | | Panel 2 – RP+8 Hours | 100% (30/30) | 88.6% - 100% | | Overall Agreement (All Targets/Sample Types) | | | 100% (180/180) | 97.9% - 100% | Confidential & Restricted 510(k) Summary Page 12 of 43 {17} Diasorin LIAISON PLEX® Gram-Positive Blood Culture Assay Traditional 510(k) # Lot-to-lot Reproducibility Lot-to-lot reproducibility of the LIAISON PLEX® BCP Assay was evaluated by one operator over a minimum of five non-consecutive days across three lots of LIAISON PLEX® BCP Assay cartridges and four LIAISON PLEX® systems. The same reproducibility panel of six blood culture samples; two representative on-panel organisms (Staphylococcus aureus and Enterococcus faecalis) individually cultured at ring positivity, and eight hours after ring positivity, one negative sample contrived with an off-panel organism (Escherichia coli), and one negative blood culture matrix (NBM) sample, were prepared and tested for the evaluation of the lot-to-lot reproducibility. Each sample type was tested in triplicate per cartridge lot on a given testing day. Lot-to-lot reproducibility of the LIAISON PLEX® BCP Assay cartridges was 100%, and results are summarized in Table 3. Table 3: LIAISON PLEX® Gram-Positive Blood Culture (BCP) Assay Lot-to-Lot Reproducibility Results | Organism ID | Reportable Targets | Sample Type | Reagent Lot | Results (% agreement) | Results (95% CI) | | --- | --- | --- | --- | --- | --- | | Staphylococcus aureus | Staphylococcus spp. S. aureus | Panel 1 – RP | Lot 1 | 100% (15/15) | 79.6% - 100% | | | | | Lot 2 | 100% (15/15) | | | | | | Lot 3 | 100% (15/15) | | | | | | Overall | 100% (45/45) | 92.1% – 100% | | | | Panel 1 – RP+8 Hours | Lot 1 | 100% (15/15) | 79.6% - 100% | | | | | Lot 2 | 100% (15/15) | | | | | | Lot 3 | 100% (15/15) | | | | | | Overall | 100% (45/45) | 92.1% – 100% | | Enterococcus faecalis | Enterococcus faecalis | Panel 2 – RP | Lot 1 | 100% (15/15) | 79.6% - 100% | | | | | Lot 2 | 100% (15/15) | | | | | | Lot 3 | 100% (15/15) | | | | | | Overall | 100% (45/45) | 92.1% – 100% | | | | Panel 2 – RP+8 Hours | Lot 1 | 100% (15/15) | 79.6% - 100% | | | | | Lot 2 | 100% (15/15) | | | | | | Lot 3 | 100% (15/15) | | | | | | Overall | 100% (45/45) | 92.1% – 100% | | Escherichia coli | None | Contrived Negative | Lot 1 | 100% (15/15) | 79.6% - 100% | | | | | Lot 2 | 100% (15/15) | | | | | | Lot 3 | 100% (15/15) | | | | | | Overall | 100% (45/45) | 92.1% – 100% | | No Target | None | Negative Blood Matrix | Lot 1 | 100% (15/15) | 79.6% - 100% | | | | | Lot 2 | 100% (15/15) | | | | | | Lot 3 | 100% (15/15) | | | | | | Overall | 100% (45/45) | 92.1% – 100% | | Resistance Marker | | | | | | | Staphylococcus aureus | mecA/C | Panel 1 – RP | Lot 1 | 100% (15/15) | 79.6% - 100% | | | | | Lot 2 | 100% (15/15) | | | | | | Lot 3 | 100% (15/15) | | | | | | Overall | 100% (45/45) | 92.1% – 100% | | | | Panel 1 – RP+8 Hours | Lot 1 | 100% (15/15) | 79.6% - 100% | | | | | Lot 2 | 100% (15/15) | | | Lot 3 | 100% (15/15) | | | | | Confidential & Restricted 510(k) Summary {18} Diasorin LIAISON PLEX® Gram-Positive Blood Culture Assay Traditional 510(k) | | | | Overall | 100% (45/45) | 92.1% – 100% | | --- | --- | --- | --- | --- | --- | | Enterococcus faecalis | vanB | Panel 2 – RP | Lot 1 | 100% (15/15) | 79.6% - 100% | | | | | Lot 2 | 100% (15/15) | | | | | | Lot 3 | 100% (15/15) | | | | | | Overall | 100% (45/45) | 92.1% – 100% | | | | Panel 2 – RP+8 Hours | Lot 1 | 100% (15/15) | 79.6% - 100% | | | | | Lot 2 | 100% (15/15) | | | | | | Lot 3 | 100% (15/15) | | | | | | Overall | 100% (45/45) | 92.1% – 100% | b. Linearity/assay reportable range: Not applicable. The LIAISON® PLEX Gram-Positive Blood Culture Assay is a qualitative assay. Confidential & Restricted 510(k) Summary {19} Diasorin LIAISON PLEX® Gram-Positive Blood Culture Assay Traditional 510(k) c. 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® Gram-Positive Blood Culture Assay cartridge includes internal controls to ensure performance of sample preparation and detection. The internal extraction control is present in the lysis tube when the sample is added. Sample preparation is initiated and the extraction control assesses extraction, nucleic acid recovery, and detection. Finally, addition of a post-extraction hybridization control serves as an indicator of successful hybridization. Internal control results are reported as Pass or Fail on the printed reports (see Table 4 for detailed explanations of each control result). Internal controls must generate a signal above threshold in each internal reaction for the system to report a valid test result. Table 4. Interpretation of Controls on the LIAISON PLEX® Gram-Positive Blood Culture Assay Report | Internal Control Result | Explanation | Suggested Action | | --- | --- | --- | | Pass | Test was completed and internal controls were successful, indicating that valid results were generated. | Review and report results | | Fail | One or more internal control failed. | Repeat test with a new cartridge | ## External Controls Positive and negative external controls should be tested with each new lot or shipment of reagents, or monthly, (whichever occurs first), or in accordance with updated local, regional, state, and/or federal guidelines. Verified negative blood matrix can be used as the negative control. Previously characterized positive samples or verified negative blood matrix spiked with well characterized organisms may be used as the external positive control. External controls should be used in accordance with laboratory protocols and in accordance with local, state, and federal accrediting organizations, as applicable. ## Stability ## Specimen Stability Performance of the LIAISON PLEX® Gram-Positive Blood Culture (BCP) Assay was assessed using specimens tested in a fresh state (at bottle/ring positive and at bottle/ring positive + 8 hours) and after exposure to various storage conditions. Conditions tested included refrigerated storage (2° to 8°C) and room temperature storage (15°C to 30°C) to span the typical "fresh specimen" storage conditions across multiple time points. Positive specimens containing five target organisms representing a total of 9 reportable gram-positive targets Confidential & Restricted 510(k) Summary {20} Diasorin LIAISON PLEX® Gram-Positive Blood Culture Assay Traditional 510(k) and select resistance markers were tested as well as negative blood matrix control specimen containing no target organisms. 100% detection of all reportable targets was observed across all timepoints. The negative sample demonstrated 0% positivity across all time-points and storage conditions tested. The results demonstrated that specimens may be stored under the following temperature conditions without impacting the performance of the LIAISON PLEX® BCP cartridge: - Up to 72 hours (3 days) at Refrigerated (2-8°C) or Room Temperature (15-30°C) storage conditions. ## Device Stability A shelf-life study was conducted to evaluate the real-time stability of the LIAISON PLEX® BCP Assay at the recommended storage conditions of room temperature (15°C – 30°C). Real-time stability was assessed using three Positive Control panels which interrogate representative targets in the assay, and one Negative Control which consisted of negative blood matrix. Results of real-time stability for all tested lots demonstrated the LIAISON PLEX® BCP Assay is stable for at least 1 month when stored at 15°C – 30°C, and up to 3 months when stored at 15°C – 30°C for two of the three cartridge lots evaluated. Testing for the third lot is ongoing. Shelf-life will be extended based upon results of on-going stability testing. An open box stability study was performed to evaluate the stability of the LIAISON PLEX® BCP Assay cartridges at room temperature once removed from their foil pouch. Testing was performed shortly after kits were manufactured and will be repeated at the end of the product shelf-life. Non-aged cartridges were tested at 0 hours (T0), 3 hours (T1), and 9 hours (T2) after removal from their pouch. Each time point included testing of three Positive Control panels which interrogate seven reportable targets in the assay, and one Negative Control which consisted of negative blood matrix. One unexpected result (false positive) for Staphylococcus lugdunensis and Streptococcus spp. occurred for a negative target. Expected results were observed at all other timepoints and conditions. Results of open-box stability indicate the cartridges are stable for up to nine hours after cartridges are removed from their foil pouches and stored at room temperature. ## Fresh vs. Frozen Specimen Stability A fresh vs. frozen specimen stability study was performed to evaluate the performance of the LIAISON PLEX® Gram-Positive Blood Culture (BCP) assay in specimens that have been prepared "fresh" (at two growth durations referred to as Bottle/Ring Positive and Bottle/Ring Positive + 8 hours) and subjected to a defined number of freeze/thaw (F/T) cycles as well as those experiencing a prolonged storage in frozen conditions. The study was performed using six representative organisms detected by the LIAISON PLEX® BCP Assay cultured individually in blood culture bottles. Performance testing using negative blood matrix served as a control test during the study. Material was tested under 5 different conditions – Material was tested at multiple freeze thaw cycles: 1st Freeze-thaw, 2nd Freeze-thaw, and 3rd Freeze-thaw, and was frozen for a minimum of 8 hours in between each freeze-thaw cycle. In the prolonged testing, material was frozen at time points of 15 days and 30 days. A total of 701 replicates were included in this study. The results Confidential & Restricted 510(k) Summary Page 16 of 43 {21} Diasorin LIAISON PLEX® Gram-Positive Blood Culture Assay Traditional 510(k) demonstrated 100% positivity for target positive samples at both growth durations and all freeze-thaw conditions. The negative blood matrix demonstrated 0% positivity of all reportable targets for the assay at all freeze-thaw conditions. ## d. Growth and Detection Study The growth and detection study was performed to evaluate detection of each organism at the time of culture positivity and 8 hours after culture positivity for the organisms listed in Table 5. Three bottles for each organism were grown to ring positive or 8 hours after ring positive and three replicates were tested for each bottle, for a total of 9 replicates tested per organism. The results, presented in Table 5, demonstrated 100% positivity for target positive samples and 0% positivity when tested with negative blood. Table 5. LIAISON PLEX® Gram-Positive Blood Culture Assay Growth & Detection Results Summary | Organism Tested | Expected Targets | Ring Positivity | 8 Hours After Ring Positivity | | --- | --- | --- | --- | | Per Bottle (CFU/mL) | Positive Agreement/ Total (% Detected) | Per Bottle (CFU/mL) | Positive Agreement/ Total (% Detected) | | Bacillus subtilis ATCC 19659 | Bacillus spp. | 1.29E+08 | 9/9 (100%) | 3.57E+05 | 9/9 (100%) | | 6.10E+08 | 4.97E+05 | | 3.60E+08 | 2.90E+05 | | Enterococcus faecium ATCC 700221 | Enterococcus faecium | vanA | 2.37E+08 | 9/9 (100%) | 9.30E+08 | 12/12 (100%)^{a} | | 3.01E+08 | 7.80E+08 | | 2.24E+08 | 9.30E+08 | | Enterococcus faecalis ATCC 51575 | Enterococcus faecalis | vanB | 6.87E+08 | 9/9 (100%) | 2.90E+09 | 9/9 (100%) | | 9.27E+08 | 2.80E+09 | | 9.83E+08 | 2.57E+09 | | Listeria monocytogenes ATCC 15313 | Listeria spp. | 7.57E+08 | 9/9 (100%) | 6.40E+08 | 9/9 (100%) | | 9.63E+08 | 4.33E+08 | | 7.73E+08 | 8.17E+08 | | Staphylococcus aureus ATCC BAA-2312 | Staphylococcus spp. | Staphylococcus aureus | mecA/mecC | 1.52E+07 | 9/9 (100%) | 3.80E+08 | 9/9 (100%) | | 2.34E+07 | 4.10E+08 | | 1.88E+07 | 1.30E+08 | | Staphylococcus epidermidis ATCC 35984 | Staphylococcus spp. | Staphylococcus epidermidis | mecA/mecC | 1.55E+08 | 9/9 (100%) | 1.40E+09 | 9/9 (100%) | | 4.40E+08 | 1.48E+09 | | 2.84E+08 | 1.52E+09 | | Staphylococcus lugdunensis ATCC 49576 | Staphylococcus lugdunensis ATCC 49576 | 5.67E+08 | 9/9 (100%) | 2.83E+08 | 9/9 (100%) | | 7.43E+08 | 2.92E+08 | | 8.90E+08 | 2.65E+08 | | Streptococcus agalactiae ATCC 12386 | Streptococcus spp. | Streptococcus | 1.21E+09 | 9/9 (100%) | 1.69E+09 | 9/9 (100%) | | 1.32E+09 | 1.48E+09 | Confidential & Restricted 510(k) Summary {22} Diasorin LIAISON PLEX® Gram-Positive Blood Culture Assay Traditional 510(k) | Organism Tested | Expected Targets | Ring Positivity | 8 Hours After Ring Positivity | | --- | --- | --- | --- | | Per Bottle (CFU/mL) | Positive Agreement/ Total (% Detected) | Per Bottle (CFU/mL) | Positive Agreement/ Total (% Detected) | | | agalactiae | 1.12E+09 | | 2.03E+09 | | | Streptococcus anginosus ATCC 33397 | Streptococcus spp. | Streptococcus anginosus group | 7.57E+08 | 9/9 (100%) | 3.30E+06 | 9/9 (100%) | | 4.97E+08 | 6.13E+06 | | 3.63E+08 | 1.90E+07 | | Streptococcus pneumoniae ATCC 49619 | Streptococcus spp. | Streptococcus pneumoniae | 8.30E+08 | 9/9 (100%) | 1.35E+07 | 9/9 (100%) | | 8.40E+08 | 1.92E+07 | | 9.80E+08 | 1.54E+08 | | Streptococcus pyogenes ATCC 700294 | Streptococcus spp. | Streptococcus pyogenes | 3.43E+08 | 9/9 (100%) | 7.60E+08 | 9/9 (100%) | | 3.40E+08 | 5.00E+08 | | 4.70E+08 | 4.10E+08 | | Organism Tested | Expected Targets | Ring Negative | | Negative Blood | None | 0/3 (0%) | a False Positive Bacillus spp. result in one replicate. Three additional replicates were tested and no additional FPs were observed. ## e. Analytical Reactivity (Inclusivity) The analytical reactivity (inclusivity) of the LIAISON PLEX® BCP Assay was evaluated by using a collection of 184 isolates, representing the genetic diversity of the analytes included as part of the LIAISON PLEX® BCP Assay. Table 6 contains the summary of the organisms tested and the genus and species detected by the LIAISON PLEX® BCP Assay. Table 7 contains the summary for the antimicrobial resistance marker reportable targets also detected by the assay. Table 6: LIAISON PLEX® Gram-Positive Blood Culture (BCP) Inclusivity Summary (Microorganism Markers) | Reportable Target (Genus) | Reportable Target (Species) | Organism | # of strains | % Detected | | --- | --- | --- | --- | --- | | Bacillus spp. | N/A | Bacillus cereus | 4 | 100% | | | | Bacillus licheniformis | 2 | 100% | | | | Bacillus subtilis | 3 | 100% | | | | Bacillus thuringiensis | 2 | 100% | | N/A | Enterococcus faecalis | Enterococcus faecalis | 9 | 100% | | | Enterococcus faecium | Enterococcus faecium | 9 | 100% a | | Listeria spp. | N/A | Listeria grayi | 2 | 100% | | | | Listeria innocua | 2 | 100% | | | | Listeria ivanovii | 2 | 100% | | | | Listeria monocytogenes | 6 | 100% | | | | Listeria seeligeri | 2 | 100% | Confidential & Restricted 510(k) Summary {23} Diasorin LIAISON PLEX® Gram-Positive Blood Culture Assay Traditional 510(k) | Reportable Target (Genus) | Reportable Target (Species) | Organism | # of strains | % Detected | | --- | --- | --- | --- | --- | | | | Listeria welshimeri | 2 | 100% | | Staphylococcus spp. | S. aureus | Staphylococcus aureus | 43 | 100% | | S. epidermidis | Staphylococcus epidermidis | 8 | 100% | | S. lugdunensis | Staphylococcus lugdunensis | 5 | 100% | | N/A | Staphylococcus argenteus | 2 | 100%^{b} | | Staphylococcus auricularis | 2 | 100% | | Staphylococcus capitis | 2 | 100% | | Staphylococcus caprae | 1 | 100% | | Staphylococcus cohnii | 2 | 100% | | Staphylococcus haemolyticus | 2 | 100% | | Staphylococcus hominis | 3 | 100% | | Staphylococcus intermedius | 2 | 100% | | Staphylococcus mucosae | 1 | 100%^{c} | | Staphylococcus pasteuri | 1 | 100% | | Staphylococcus saccharolyticus | 3 | 100% | | Staphylococcus saprophyticus | 2 | 100% | | Staphylococcus schleiferi | 1 | 100% | | Mammaliicoccus (Staphylococcus) sciuri | 2 | 100% | | Staphylococcus simulans | 2 | 100% | | Staphylococcus warneri | 2 | 100% | | Staphylococcus xylosus | 1 | 100% | | Streptococcus spp. | S. agalactiae | Streptococcus agalactiae | 5 | 100% | | S. anginosus Group | Streptococcus anginosus | 2 | 100% | | Streptococcus constellatus | 3 | 100% | | Streptococcus intermedius | 2 | 100% | | S. pneumoniae | Streptococcus pneumoniae | 5 | 100% | | S. pyogenes | Streptococcus pyogenes | 5 | 100% | | N/A | Streptococcus bovis | 3 | 100% | | Streptococcus dysgalactiae | 2 | 100% | | Streptococcus equi | 2 | 100% | | Streptococcus equinus | 2 | 100% | | Streptococcus gallolyticus | 3 | 100% | | Streptococcus gordonii | 2 | 100% | | Streptococcus infantarius subsp. coli | 1 | 100% | | Streptococcus infantis | 2 | 100% | | Streptococcus mitis | 2 | 100% | | Streptococcus mutans | 2 | 88.9%^{d} | | Streptococcus oralis | 2 | 100% | | Streptococcus parasanguinis | 2 | 100% | Confidential & Restricted 510(k) Summary Page 19 of 43 {24} Diasorin LIAISON PLEX® Gram-Positive Blood Culture Assay Traditional 510(k) | Reportable Target (Genus) | Reportable Target (Species) | Organism | # of strains | % Detected | | --- | --- | --- | --- | --- | | | | Streptococcus peroris | 1 | 100% | | | | Streptococcus pseudopneumoniae | 1 | 100% | | | | Streptococcus salivarius | 1 | 100% | | | | Streptococcus sanguinis | 2 | 100% | a One replicate from one strain resulted in a false positive (FP) S. lugdunensis result, three additional replicates were run for that strain. No additional FPs were observed. b Staphylococcus argenteus cross reacts with S. aureus. c Staphylococcus muscae cross reacts with Listeria spp. d One strain of Streptococcus mutans, ATCC 25175, was not detected as Streptococcus spp. in one of three initial replicates tested. Three additional replicates were run, giving an overall detection rate for Streptococcus spp. of 5/6 for that strain. S. mutans strain 31383 was fully detected in all replicates. Table 7: LIAISON PLEX® Gram-Positive Blood Culture (BCP) Inclusivity Summary – Antimicrobial Resistance Markers | Reportable Target (Resistance Marker) | Organism | # of strains | % Detected | | --- | --- | --- | --- | | mecA/C | Staphylococcus argenteus | 1 | 100% | | mecA/C | Staphylococcus aureus | 35 | 100% | | | Staphylococcus epidermidis | 5 | 100% | | | Staphylococcus hominis | 1 | 100% | | | Mammaliicoccus (Staphylococcus) sciuri | 2 | 100% | | vanA | Enterococcus faecalis | 3 | 100% | | | Enterococcus faecium | 3 | 100%^{a} | | vanB | Enterococcus faecalis | 3 | 100% | | | Enterococcus faecium | 3 | 100% | a One replicate from one strain resulted in a false positive (FP) S. lugdunensis result, and three additional replicates were run for that strain. No additional FPs were observed. ## Predicted (in silico) Reactivity (Inclusivity) Results For all targets, in silico inclusivity analysis was performed using sequences available in the GenBank and WGS (whole genome shotgun) databases from March to April 2024. Alignments of the signal fragment for each target were generated using MAFFT (version 7.490). For all targets, the inclusivity analysis involved assessing the percent homology of each oligo sequence to its binding region on each target sequence retrieved from the public databases. The predicted inclusivity based on sequence homology is the percentage of sequences with at least 90% oligo identity. In determining oligo identity, the highest percent identity of each oligo in the same component was assessed and then the lowest percent identity of the two components (capture and mediator probes) is used to characterize the inclusivity of the sequence. In silico analysis results are summarized below in Table 8. Confidential & Restricted 510(k) Summary {25} Diasorin LIAISON PLEX® Gram-Positive Blood Culture Assay Traditional 510(k) Table 8 – In silico Analysis Results | Reportable Target | Inclusive Organism/Target | Total # Sequences in Alignment | # Sequences with Percent Oligo Identity ≥ 90% | Predicted Inclusivity Percentage (%) | | --- | --- | --- | --- | --- | | Bacillus spp. a | Bacillus cereus group | 6722 | 6718 | 100 | | | Bacillus subtilis group | 4320 | 4318 | 100 | | Enterococcus faecalis | Enterococcus faecalis | 746 | 745 | 100 | | Enterococcus faecium | Enterococcus faecium | 555 | 555 | 100 | | Listeria spp. b | Listeria monocytogenes | 8812 | 8812 | 100 | | | other Listeria species | 899 | 876 | 97 | | Staphylococcus aureus | Staphylococcus aureus | 2307 | 2307 | 100 | | Staphylococcus epidermidis | Staphylococcus epidermidis | 250 | 250 | 100 | | Staphylococcus lugdunensis | Staphylococcus lugdunensis | 162 | 162 | 100 | | Staphylococcus spp. c | Staphylococcus spp. | 13355 | 13354 | 100 | | Streptococcus agalactiae | Streptococcus agalactiae | 454 | 454 | 100 | | Streptococcus anginosus Group | Streptococcus anginosus | 356 | 356 | 100 | | | Streptococcus constellatus | 70 | 70 | 100 | | | Streptococcus intermedius | 127 | 127 | 100 | | | unspecified species from Streptococcus anginosus group | 7 | 7 | 100 | | Streptococcus pneumoniae | Streptococcus pneumoniae | 693 | 693 | 100 | | Streptococcus pyogenes | Streptococcus pyogenes | 732 | 732 | 100 | | Streptococcus spp. d | Streptococcus spp. | 23589 | 23574 | 100 | | mecA/mecC e | mecA | 2201 | 2158 | 98 | | | mecC | 32 | 32 | 100 | | vanA f | vanA | 570 | 551 | 97 | | vanB f | vanB | 215 | 215 | 100 | a Includes sequences for 26 species of B. cereus group and 15 species of B. subtilis group. Oligo designs may also detect Bacillus species that are not part of these two groups. b Includes sequences for 28 Listeria species. c Includes sequences for 44 Staphylococcus species. d Includes sequences for 108 Streptococcus species. e Includes sequences for Staphylococcus species only. f Includes sequences for E. faecalis and E. faecium only. f. Analytical Specificity (Exclusivity) Cross-Reactivity The analytical specificity study was performed to evaluate cross-reactivity of the LIAISON PLEX® BCP Assay with "off-panel" organisms, including both phylogenetically related to the on-panel organisms and organisms likely to be present in typical blood culture samples. Table 9 contains the summary for the genus and species reportable targets. Out Confidential & Restricted 510(k) Summary {26} Diasorin LIAISON PLEX® Gram-Positive Blood Culture Assay Traditional 510(k) of the 103 off-panel species tested, 97 resulted in no cross-reactivity, 5 resulted in cross-reactivity with one reportable target, and 1 organism resulted in positivity for 1 out of 6 replicates tested. Organisms with cross-reactivity and the BCP target that was detected are listed in Table 10. Table 9: LIAISON PLEX® BCP Assay Analytical Specificity (Cross Reactivity) Summary | Organism | Positivity | Organism | Positivity | | --- | --- | --- | --- | | Gram Positive | | | | | Abitrophia defectiva | 0% | Enterococcus flavescens | 0% | | Aerococcus viridans | 0% | Enterococcus gallinarum, vanC | 0% | | Arcanobacterium bernardiae | 0% | Enterococcus hirae | 0% | | Arcanobacterium haemolyticum | 0% | Enterococcus mundtii | 0% | | Corynebacterium amycolatum | 0% | Enterococcus raffinosus | 0% | | Corynebacterium diphtheriae | 0% | Erysipelothrix rhusiopathiae | 0% | | Corynebacterium flavescens | 0% | Kocuria kristinae | 0% | | Corynebacterium genitalium | 0% | Kytococcus sedentarius, methicillin resistant | 0% | | Corynebacterium glutamicum | 0% | Lactobacillus acidophilus | 0% | | Corynebacterium jeikeium | 0% | Lactobacillus crispatus | 0% | | Corynebacterium pseudodiptherticum | 0% | Lactobacillus rhamnosus | 0% | | Corynebacterium renale | 0% | Leuconostoc carnosum | 100% | | Corynebacterium striatum | 0% | Leuconostoc mesenteroides | 0% | | Corynebacterium urealyticum | 0% | Pediococcus acidilactici | 0% | | Cutibacterium acnes | 0% | Pediococcus pentosaceus | 0% | | Cutibacterium avidum | 0% | Peptostreptococcus anaerobius | 0% | | Propionibacterium freudenreichii | 0% | Planococcus citreus | 0% | | Enterococcus avium | 100% | Planococcus kocurii | 0% | | Enterococcus casseliflavis, VRE, vanC | 0% | Rothia dentocariosa | 0% | | Enterococcus dispar | 0% | Rothia (Stomatococcus) mucilaginosa | 0% | | Enterococcus durans | 0% | | | | Gram Negative | | | | | Acinetobacter calcoaceticus | 0% | Haemophilus influenzae | 0% | | Acinetobacter pittii | 0% | Herbaspirillum huttiense | 0% | | Aggregatibacter aphrophilus | 100% | Kingella kingae | 0% | | Bacteroides fragilis | 0% | Klebsiella oxytoca | 0% | | Brevundimonas diminuta | 0% | Klebsiella pneumoniae | 0% | | Burkholderia cepacia | 0% | Klebsiella variicola | 0% | | Capnocytophaga ochracea | 0% | Leclercia adecarboxylata | 0% | | Cardiobacterium hominis | 0% | Moraxella catarrhalis | 0% | | Cedecea lapagei | 0% | Morganella morganii | 0% | | Citrobacter amalonaticus | 0% | Neisseria lactamica | 0% | Confidential & Restricted 510(k) Summary {27} Diasorin LIAISON PLEX® Gram-Positive Blood Culture Assay Traditional 510(k) | Organism | Positivity | Organism | Positivity | | --- | --- | --- | --- | | Citrobacter freundii | 0% | Neisseria meningitidis | 0% | | Comamonas testosteroni | 0% | Neisseria mucosa | 0% | | Delftia acidovorans | 0% | Neisseria sicca | 0% | | Eikenella corrodens | 0% | Parabacteroides distasonis | 0% | | Elizabethkingia meningoseptica | 0% | Pasteurella aerogenes | 0% | | Enteric Group 137 | 0% | Prevotella bivia | 0% | | Enterobacter aerogenes | 0% | Proteus mirabilis | 0% | | Enterobacter cloacae | 0% | Proteus penneri | 100% | | Enterobacter hormaechei | 0% | Proteus vulgaris | 100% | | Escherichia albertii | 0% | Pseudomonas aeruginosa | 0% | | Escherichia coli | 0% | Pseudomonas alcaligenes | 0% | | Escherichia fergusonii | 0% | Raoultella ornithinolytica | 0% | | Escherichia hermannii | 0% | Salmonella enterica | 0% | | Fusobacterium necrophorum | 0% | Serratia marcescens | 0% | | Fusobacterium nucleatum | 0% | Stenotrophomonas maltophilia | 0% | | Haemophilus haemolyticus | 0% | | | | Yeast/Fungi | | | | | Aspergillus fumigatus | 0% | Cryptococcus neoformans | 0% | | Candida albicans | 0% | Debaryomyces hansenii (Candida famata) | 0% | | Nakaseomyces glabratus (Candida glabrata) | 0% | Kluyveromyces lactis | 0% | | Pichia kudriavzevii (Candida krusei) | 0% | Saccharomyces cerevisiae | 0% | | Candida parapsilosis | 16.7%^{a} | Schizosaccharomyces pombe | 0% | | Candida tropicalis | 0% | | | a Initial testing results showed 1 of 3 replicates detected as S. lugdunensis. An additional 3 replicates were tested (for a total of 6 replicates) and no additional false positives were seen. Table 10: LIAISON PLEX® BCP Assay Analytical Specificity (Cross Reactivity) Summary | Cross-Reactive Organism | BCP Target Detected | | --- | --- | | Enterococcus avium | Enterococcus faecium | | Leuconostoc carnosum | Streptococcus spp. | | Aggregatibacter aphrophilus | Streptococcus spp. | | Proteus penneri | Streptococcus spp. | | Proteus vulgaris | Streptococcus spp. | Confidential & Restricted 510(k) Summary {28} Diasorin LIAISON PLEX® Gram-Positive Blood Culture Assay Traditional 510(k) In Silico Cross-Reactivity For in silico exclusivity assessment of the oligo sequences incorporated in the assay designs against on-panel and off-panel organisms listed in Table 11, based on analysis of sequences available in the GenBank nt database as of July 27, 2024, the following potential cross-reactivity is predicted: - Some strains of Enterococcus durans and 3 strains of Streptococcus species (AY123726.1, FJ577604.1, MK608388.1) are predicted to produce false positive Enterococcus faecalis results. - One strain of Enterococcus durans (KT877992.1), 1 strain of Enterococcus faecalis (CP092577.1) and some strains Enterococcus avium are predicted to produce false positive Enterococcus faecium results. - Staphylococcus aureus oligo designs are predicted to detect some strains of Staphylococcus argenteus and one strain of Staphylococcus schweitzeri (LR134304.1). - Staphylococcus spp. oligo designs are predicted to detect some strains of Macrococcoides caseolyticum. - Some strains of Streptococcus species (S. lactarius, S. milleri, S. oralis, S. periodonticum, S. pneumoniae, S. rubneri, S. vaginalis) are predicted to produce false positive Streptococcus anginosus Group results. - Streptococcus pneumoniae oligo designs are predicted to detect a few strains of various Streptococcus species (S. downii, S. mitis, S. oralis). - Some strains of Aggregatibacter aphrophilus, unspecified Bacillus species, Enterococcus species (E. durans, E. gallinarum), Glaesserella parasuis, Haemophilus species (H. ducreyi, H. influenzae, H. parahaemolyticus, H. parainfluenzae), Lactococcus species (L. garvieae, L. lactis), Leuconostoc carnosum, Moellerella wisconsensis, Morganella morganii, Pasteurella multocida, Proteus species (P. appendicitidis, P. columbae, P. faecis, P. penneri, P. terrae, P. vulgaris), Providencia species (P. alcalifaciens, P. hangzhouensis, P. heimbachae, P. huaxiensis, P. manganoxydans, P. rettgeri, P. rustigianii, P. stuartii, P. vermicola, P. zhijiangensis), Serratia species (S. marcescens, S. symbiotica) and Xenorhabdus species (X. bovienii, X. hominickii, X. nematophila) are predicted to produce false positive Streptococcus spp. results. - Listeria spp. oligo designs are predicted to detect some strains of Staphylococcus muscae. Table 11: Potential Cross-Reactive Organisms assessed in the In Silico Exclusivity Analysis | On-Panel Organisms | Off-Panel Organisms | | | | | --- | --- | --- | --- | --- | | | Gram-Positive Bacteria | Gram-Negative Bacteria | Resistance Markers | Yeasts / Viruses / Parasites | | Bacillus spp. | Abiotrophia defectiva | Acinetobacter spp. | AmpC | Aspergillus flavus | | Enterococcus faecalis | Actinomyces israelii | Actinobacillus hominis | CMY | Aspergillus fumigatus | | Enterococcus faecium | Actinomyces naeslundii | Actinobacillus ureae | CTX-M | Aspergillus niger | | Listeria spp. | Actinomyces odontolyticus | Aeromonas caviae | IMP | Aspergillus terreus | | Staphylococcus aureus | Aerococcus sanguinicola | Aeromonas hydrophila | KPC | Blastomyces dermatitidis | | Staphylococcus epidermidis | Aerococcus urinae | Aeromonas sobria | MCR | Candida albicans | | Staphylococcus lugdunensis | Aerococcus viridans | Aggregatibacter actinomycetemcomitans | NDM | Candida auris | | Staphylococcus spp. | Arcanobacterium bernardiae | Aggregatibacter aphrophilus | ompK36 | Candida dubliniensis | | Streptococcus agalactiae | Arcanobacterium haemolyticum | Bacteroides caccae | OXA | Candida famata | | Streptococcus anginosus group | Arthrobacter psychrolactophilus | Bacteroides fragilis | RAHN | Candida glabrata | Confidential & Restricted 510(k) Summary {29} Diasorin LIAISON PLEX® Gram-Positive Blood Culture Assay Traditional 510(k) | On-Panel Organisms | Off-Panel Organisms | | | | | --- | --- | --- | --- | --- | | | Gram-Positive Bacteria | Gram-Negative Bacteria | Resistance Markers | Yeasts / Viruses / Parasites | | Streptococcus pneumoniae | Brochothrix thermosphacta | Bacteroides ovatus | SHV | Candida guilliermondii | | Streptococcus pyogenes | Carnobacterium divergens | Bacteroides thetaiotaomicron | SME | Candida haemulonii | | Streptococcus spp. | Carnobacterium maltaromaticum | Bacteroides uniformis | SPM | Candida inconspicua | | mecA | Cellulomonas turbata | Bacteroides vulgatus | TEM | Candida kefyr | | mecC | Cellulosimicrobium cellulans | Bacteroides xylanisolvens | vanC | Candida krusei | | vanA | Clostridioides difficile | Bordetella bronchiseptica | vanD | Candida lipolytica | | vanB | Clostridium bifermentans | Bordetella parapertussis | vanM | Candida lusitaniae | | | Clostridium clostridioforme | Bordetella pertussis | VIM | Candida metapsilosis | | | Clostridium perfringens | Brevundimonas diminuta | | Candida multis-gemmis | | | Clostridium ramosum | Brevundimonas vesicularis | | Candida nivariensis | | | (Thomasclavelia ramosa) | | | | | | Clostridium septicum | Burkholderia cepacia | | Candida norvegensis | | | Clostridium tertium | Burkholderia mallei | | Candida orthopsilosis | | | Clostridium tetani | | | | | | Corynebacterium spp. | Burkholderia multivorans | | Candida parapsilosis | | | Cutibacterium acnes | | | | | | Cutibacterium avidum | Burkholderia pseudomallei | | Candida sojae | | | Cutibacterium granulosum | Campylobacter hominis | | Candida tropicalis | | | Enterococcus avium | Capnocytophaga ochracea | | Candida duobushaemulonii | | | Enterococcus casseliflavus | Cardiobacterium hominis | | Candida viswanathii | | | Enterococcus cecorum | Chlamydia trachomatis | | Coccidioides immitis | | | Enterococcus dispar | Chlamydophila pneumoniae | | Coccidioides posadasii | | | Enterococcus durans | Chromobacterium violaceum | | Cryptococcus amylolentus | | | Enterococcus flavescens | Citrobacter spp. | | Cryptococcus gattii | | | Enterococcus gallinarum | Comamonas testosteroni | | Cryptococcus neoformans | | | Enterococcus hirae | Delftia acidovorans | | Cryptococcus uniguttulatus | | | Enterococcus mundtii | Eikenella corrodens | | Cutaneotrichosporon curvatum | | | Enterococcus raffinosus | Elizabethkingia meningoseptica | | Cyberlindnera fablianii | | | Erysipelothrix rhusiopathiae | Enterobacter spp. | | Geotrichum capitatum (Magnusiomyces capitatus) | | | Finegoldia magna | Enterobacteriaceae | | Histoplasma capsulatum | | | Gemella haemolysans | Escherichia coli | | Kluyveromyces lactis | | | Gemella morbillorum | Fusobacterium necrophorum | | Kodamaea ohmeri | | | Globicatella spp. | Fusobacterium nucleatum | | Lodderomyces elongisporus | | | Granulicatella adiacens | Haemophilus influenzae | | Magnusiomyces capitatus | | | Granulicatella elegans | Haemophilus aegyptius | | Millerozyma farinosa | | | Kocuria kristinae | Haemophilus ducreyi | | Naganishia albida | | | Kocuria rhizophila | Haemophilus haemolyticus | | Papiliotrema laurentii | | | Kytococcus sedentarius | Haemophilus parahaemolyticus | | Penicillium chrysogenum | | | Lactobacillus acidophilus | Haemophilus parainfluenzae | | Rhodotorula mucilaginosa | | | Lactobacillus crispatus | Haemophilus parasuis | | Saccharomyces cerevisiae | Confidential & Restricted 510(k) Summary {30} Diasorin LIAISON PLEX® Gram-Positive Blood Culture Assay Traditional 510(k) | On-Panel Organisms | Off-Panel Organisms | | | | | --- | --- | --- | --- | --- | | | Gram-Positive Bacteria | Gram-Negative Bacteria | Resistance Markers | Yeasts / Viruses / Parasites | | | Lactobacillus rhamnosus | Haemophilus quentini | | Schizosaccharomyces pombe | | | Lactococcus garvieae | Haemophilus sputorum | | Talaromyces marneffei | | | Lactococcus lactis | Herbaspirillum huttiense | | Trichosporon asahii | | | Leuconostoc carnosum | Kingella denitrificans | | Wickerhamomyces anomalus | | | Leuconostoc citreum | Kingella kingae | | BK Virus | | | Leuconostoc mesenteroides | Kingella negevensis | | Chikungunya Virus | | | Macrococcus caseolyticus | Kingella oralis | | Cytomegalovirus | | | Micrococcus luteus | Klebsiella oxytoca | | Dengue Virus | | | Mycobacterium avium complex (MAC) | Klebsiella pneumoniae | | Enterovirus | | | Mycobacterium fortuitum | Klebsiella variicola | | Epstein Barr Virus | | | Mycobacterium mucogenicum | Legionella pneumophila | | Hepatitis A virus | | | Mycoplasma hominis | Leptospira interrogans | | Hepatitis B virus | | | Mycoplasma pneumoniae | Moraxella catarrhalis | | Hepatitis C virus | | | Nocardia farcinica | Moraxella osloensis | | Human alphaherpesvirus 1 | | | Parvimonas micra | Morganellaceae | | Human alphaherpesvirus 2 | | | Pediococcus acidilactici | Mycobacterium tuberculosis | | Human betaherpesvirus 6 | | | Pediococcus pentosaceus | Neisseria gonorrhoeae | | Human betaherpesvirus 7 | | | Peptostreptococcus anaerobius | Neisseria lactamica | | Human Immunodeficiency Virus | | | Planococcus citreus | Neisseria meningitidis | | JC Virus | | | Planococcus kocurii | Neisseria mucosa | | Measles Virus | | | Propionibacterium freudenreichii | Neisseria sicca | | Mumps Virus | | | Propionibacterium propionicum (Arachnia propionica) | Parabacteroides distasonis | | Parvovirus B19 | | | Rhodococcus equi | Parabacteroides merdae | | Rubella Virus | | | Rothia dentocariosa | Pasteurella aerogenes | | Varicella Zoster Virus | | | Rothia mucilaginosa | Pasteurella canis | | West Nile Virus | | | Sarcina ventriculi | Pasteurella multocida | | Zika Virus | | | Solibacillus silvestris | Pasteurella stomatis | | Plasmodium falciparum | | | Ureaplasma parvum | Prevotella bivia | | Trypanosoma cruzi | | | Ureaplasma urealyticum | Prevotella buccae | | | | | Vagococcus fluvialis | Prevotella denticola | | | | | Weissella paramesenteroides | Prevotella melaninogenica | | | | | | Prevotella oralis | | | | | | Proteus spp. | | | | | | Pseudomonas spp. | | | | | | Psychrobacter cryohalolentis | | | | | | Psychrobacter immobilis | | | | | | Ralstonia mannitolilytica | | | | | | Ralstonia pickettii | | | Confidential & Restricted 510(k) Summary {31} Diasorin LIAISON PLEX® Gram-Positive Blood Culture Assay Traditional 510(k) | On-Panel Organisms | Off-Panel Organisms | | | | | --- | --- | --- | --- | --- | | | Gram-Positive Bacteria | Gram-Negative Bacteria | Resistance Markers | Yeasts / Viruses / Parasites | | | | Salmonella spp. Serratia spp. Shigella spp. Stenotrophomonas acidaminiphila Stenotrophomonas maltophilia Stenotrophomonas nitritireducens Stenotrophomonas rhizophila Treponema pallidum Veillonella parvula Vibrio alginolyticus Vibrio parahaemolyticus Vibrio vulnificus | | | g. Interference ## Competitive Inhibition / Co-Infection and Microbial Interference The competitive inhibition and microbial interference study was executed to evaluate the performance of the LIAISON PLEX® BCP Assay in the presence of clinically significant levels of potential co-infections of on-panel organisms and potentially interfering (off-panel) microbes. To evaluate potential co-infections, varying ratios of two on-panel target organisms including a low titer (concentration at bottle/ring positive) and a high titer specimen (concentration at bottle/ring positive +8 hours) were tested in combination, as listed in Table 12. The on-panel target organisms were chosen to be representative of clinically relevant poly-microbial infections in blood culture specimens. To assess microbial interference, three off-panel microbes were combined in pairs with each of three representative on-panel target organisms, as listed in Table 13. These specific organism sets were chosen to mimic potentially interfering micro-organisms that are commonly found in positive blood culture samples but are not designed to be detected by the LIAISON PLEX® BCP Assay. Results are shown in Tables 12 and Table 13. On-panel targets were detected with 100% positivity for all combinations tested, both in the presence of competitive on-panel targets and in the presence of competitive off-panel pathogens. Confidential & Restricted 510(k) Summary {32} Diasorin LIAISON PLEX® Gram-Positive Blood Culture Assay Traditional 510(k) Table 12: LIAISON PLEX® BCP Assay Competitive Inhibition Summary | On-Panel High Titer Target | Positivity | On-Panel Low Titer Target | Positivity | | --- | --- | --- | --- | | Enterococcus faecalis | 100% | Staphylococcus epidermidis | 100% | | | 100% | Enterococcus faecium | 100% | | Enterococcus faecium | 100% | Staphylococcus epidermidis | 100% | | | 100% | Enterococcus faecalis | 100% | | Staphylococcus aureus | 100% | Staphylococcus epidermidis | 100% | | | 100% | Streptococcus agalactiae | 100% | | Staphylococcus epidermidis | 100% | Enterococcus faecalis | 100% | | | 100% | Enterococcus faecium | 100% | | | 100% | Staphylococcus aureus | 100% | | | 100% | Staphylococcus lugdunensis | 100% | | | 100% | Streptococcus pneumoniae | 100% | | Staphylococcus lugdunensis | 100% | Staphylococcus epidermidis | 100% | | Streptococcus agalactiae | 100% | Staphylococcus aureus | 100% | | Streptococcus pneumoniae | 100% | Staphylococcus epidermidis | 100% | Table 13: LIAISON PLEX® BCP Assay Microbial Interference Summary | On-Panel Low Titer Target | Positivity | Off-Panel High Titer Target | Positivity | | --- | --- | --- | --- | | Staphylococcus epidermidis | 100% | Escherichia coli | 0% | | | 100% | Klebsiella pneumoniae | 0% | | | 100% | Proteus mirabilis | 0% | | Enterococcus faecium | 100% | Escherichia coli | 0% | | | 100% | Klebsiella pneumoniae | 0% | | | 100% | Proteus mirabilis | 0% | | N/A | N/A | Escherichia coli | 0% | | | N/A | Klebsiella pneumoniae | 0% | | | N/A | Proteus mirabilis | 0% | ## Interfering Substances The interfering substances study was performed to evaluate the performance of the LIAISON PLEX® BCP Assay in the presence of non-microbial (endogenous and exogenous) interfering substances which may be present in blood culture specimens. Six representative "on-panel" organisms were individually tested to assess effectiveness of target detection in the presence of six typically occurring interfering substances. Each interfering substance was tested across five replicates for each organism. In addition, five replicates of a negative control was tested alongside the positive specimens to assess impact of the same interfering agents in specimens containing no target. A positive control (specimen without interfering substances) for all four targets was also tested to assess for detection capabilities. Confidential & Restricted 510(k) Summary {33} Diasorin LIAISON PLEX® Gram-Positive Blood Culture Assay Traditional 510(k) As seen in Table 14, 100% target detection was observed for all six targets without interferent and in the presence of all six interfering substances. 0% target detection was observed with the negative sample with and without interfering substances. Table 14: LIAISON PLEX® BCP Assay Interfering Substances Summary | | Organism | Interfering Substance & Tested Concentration | | | | | | | | --- | --- | --- | --- | --- | --- | --- | --- | --- | | | | Unconjugated Bilirubin | Conjugated Bilirubin | Hemoglobin | Intralipid | γ-globulin | Sodium polyanethol-sulfonate | No interferent | | | | 20 mg/dL | 20 mg/dL | 14 g/L | 3000 mg/dL | 6 g/dL | 0.25% w/v | | | % Positivity | Staphylococcus aureus | 100% | 100% | 100% | 100% | 100% | 100% | 100% | | | Staphylococcus epidermidis | 100% | 100% | 100% | 100% | 100% | 100% | 100% | | | Streptococcus pneumoniae | 100% | 100% | 100% | 100% | 100% | 100% | 100% | | | Streptococcus agalactiae | 10…
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