← Product Code [PAM](/submissions/MI/subpart-d%E2%80%94serological-reagents/PAM) · K181663 # ePlex Blood Culture Identification Panel - Gram Positive (BCID-GP) Panel (K181663) _Genmark Diagnostics, Incorporated · PAM · Dec 20, 2018 · Microbiology · SESE_ **Canonical URL:** https://fda.innolitics.com/submissions/MI/subpart-d%E2%80%94serological-reagents/PAM/K181663 ## Device Facts - **Applicant:** Genmark Diagnostics, Incorporated - **Product Code:** [PAM](/submissions/MI/subpart-d%E2%80%94serological-reagents/PAM.md) - **Decision Date:** Dec 20, 2018 - **Decision:** SESE - **Submission Type:** Traditional - **Regulation:** 21 CFR 866.3365 - **Device Class:** Class 2 - **Review Panel:** Microbiology - **Attributes:** Pediatric ## Intended Use The GenMark ePlex Blood Culture Identification Gram-Positive (BCID-GP) Panel is a qualitative nucleic acid multiplex in vitro diagnostic test intended for use on GenMark's ePlex Instrument for simultaneous qualitative detection and identification of multiple potentially pathogenic gram-positive bacterial organisms and select determinants associated with antimicrobial resistance in positive blood culture. In addition, the ePlex BCID-GP Panel is capable of detecting a wide variety of gram-negative bacteria (Pan Gram-Negative assay) and several Candida species (Pan Candida assay). The ePlex BCID-GP Panel is performed directly on blood culture samples identified as positive by a continuous monitoring blood culture system and which contain gram-positive organism. The following bacterial organisms and genes associated with antibiotic resistance are identified using the ePlex BCID-GP Panel: Bacillus cereus group, Bacillus subtilis group, Corynebacterium, Cutibacterium acnes (Propionibacterium acnes), Enterococcus, Enterococcus faecalis, Enterococcus faecium, Lactobacillus, Listeria monocytogenes, Micrococcus, Staphylococcus, Staphylococcus aureus, Staphylococcus epidermidis, Staphylococcus lugdunensis, Streptococcus, Streptococcus agalactiae (GBS), Streptococcus anginosus group, Streptococcus pneumoniae, Streptococcus pyogenes (GAS), mecA, mecC, vanA and vanB. The ePlex BCID-GP Panel contains assays for the detection of genetic determinants associated with resistance to methicillin (mecA and mecC) and vancomycin (vanA and vanB) to aid in the identification of potentially antimicrobial resistant organisms in positive blood culture samples. The antimicrobial resistance gene detected may or may not be associated with the agent responsible for disease. The ePlex BCID-GP Panel also contains targets designed to detect a broad range of organisms with a potentially misleading Gram stain result or organisms that may be missed by Gram staining altogether, for example in the case of co-infections. These include a broad Pan Gram-Negative assay as well as a Pan Candida assay, which is designed to detect four of the most prevalent Candida species: Candida albicans, Candida glabrata, Candida krusei and Candida parapsilosis. The detection and identification of specific bacterial and 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 the ePlex BCID-GP Panel 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 the ePlex BCID-GP Panel 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 ePlex BCID-GP Panel and for susceptibility testing. differentiation of mixed growth and association of antimicrobial resistance marker genes to a specific organism) and clinical presentation must be taken into consideration in the final diagnosis of blood stream infection. ## Device Story Device performs qualitative multiplex nucleic acid detection of gram-positive bacteria, resistance genes (mecA, mecC, vanA, vanB), gram-negative bacteria, and Candida species in positive blood culture samples. Input: positive blood culture sample. Process: automated cartridge-based system performs cell lysis, magnetic bead-based nucleic acid extraction, PCR/RT-PCR amplification, and electrochemical hybridization detection on a printed circuit board. Output: identification of specific pathogens and resistance markers. Used in clinical laboratories; operated by trained personnel. Output aids clinicians in rapid diagnosis and management of bloodstream infections; enables targeted antimicrobial therapy. ## Clinical Evidence Prospective multicenter study (N=711) and retrospective study (N=586) plus contrived samples (N=565). Performance compared to standard culture, MALDI-TOF, and sequencing. Sensitivity/PPA and specificity/NPA reported for all targets; overall high agreement with comparator methods. ## Technological Characteristics Cartridge-based system; nucleic acid extraction via magnetic beads; PCR/RT-PCR amplification; electrochemical detection using ferrocene-labeled signal probes and gold electrodes; ACV sensing. Standalone instrument. ## Regulatory 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 - FilmArray Blood Culture Identification Panel ([K130914](/device/K130914.md)) ## Submission Summary (Full Text) > This content was OCRed from public FDA records by [Innolitics](https://innolitics.com). If you use, quote, summarize, crawl, or train on this content, cite Innolitics at https://innolitics.com. > > Innolitics is a medical-device software consultancy. We help companies design, build, and clear FDA-regulated software and AI/ML devices, including [a 510(k)](https://innolitics.com/services/510ks/), [a De Novo](https://innolitics.com/services/regulatory/), [a SaMD](https://innolitics.com/services/end-to-end-samd/), [an AI/ML medical device](https://innolitics.com/services/medical-imaging-ai-development/), or [an FDA regulatory strategy](https://innolitics.com/services/regulatory/). {0}------------------------------------------------ Image /page/0/Picture/0 description: The image contains the logo of the U.S. Food and Drug Administration (FDA). On the left, there 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 blue square is the text "U.S. FOOD & DRUG ADMINISTRATION" in blue. December 20, 2018 GenMark Diagnostics, Incorporated Alan Maderazo VP, Quality, Regulatory & Clinical Affairs 5964 La Place Court Carlsbad, California 92008 Re: K181663 Trade/Device Name: ePlex Blood Culture Identification Panel - Gram Positive (BCID-GP) Panel 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, PEN, PEO Dated: June 22, 2018 Received: June 25, 2018 Dear Alan Maderazo: 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 (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 located 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. 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 {1}------------------------------------------------ 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 803) for devices or postmarketing safety reporting (21 CFR 4, Subpart B) for combination products (see https://www.fda.gov/CombinationProducts/GuidanceRegulatoryInformation/ucm597488.html; 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 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm. For comprehensive regulatory information about mediation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/) and CDRH Learn (http://www.fda.gov/Training/CDRHLearn). 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 (http://www.fda.gov/DICE) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100). Sincerely. # Uwe Scherf -S Uwe Scherf, M.Sc., Ph.D. Director Division of Microbiology Devices Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health Enclosure {2}------------------------------------------------ ## Indications for Use 510(k) Number (if known) K181663 #### Device Name ePlex Blood Culture Identification Gram-Positive (BCID-GP) Panel #### Indications for Use (Describe) The GenMark ePlex Blood Culture Identification Gram-Positive (BCID-GP) Panel is a qualitative nucleic acid multiplex in vitro diagnostic test intended for use on GenMark's ePlex Instrument for simultaneous qualitative detection and identification of multiple potentially pathogenic gram-positive bacterial organisms and select determinants associated with antimicrobial resistance in positive blood culture. In addition, the ePlex BCID-GP Panel is capable of detecting a wide variety of gram-negative bacteria (Pan Gram-Negative assay) and several Candida species (Pan Candida assay). The ePlex BCID-GP Panel is performed directly on blood culture samples identified as positive by a continuous monitoring blood culture system and which contain gram-positive organism. The following bacterial organisms and genes associated with antibiotic resistance are identified using the ePlex BCID-GP Panel: Bacillus cereus group, Bacillus subtilis group, Corynebacterium, Cutibacterium acnes (Propionibacterium acnes), Enterococcus, Enterococcus faecalis, Enterococcus faecium, Lactobacillus, Listeria monocytogenes, Micrococcus, Staphylococcus, Staphylococcus aureus, Staphylococcus epidermidis, Staphylococcus lugdunensis, Streptococcus agalactiae (GBS), Streptococcus anginosus group, Streptococcus pneumoniae, Streptococcus pyogenes (GAS), mecA, mecC, vanA and vanB. The ePlex BCID-GP Panel contains assays for the detection of genetic determinants associated with resistance to methicillin (mecA and mecC) and vancomycin (vanA and vanB) to aid in the identification of potentially antimicrobial resistant organisms in positive blood culture samples. The antimicrobial resistance gene detected may or may not be associated with the agent responsible for disease. The ePlex BCID-GP Panel also contains targets designed to detect a broad range of organisms with a potentially misleading Gram stain result or organisms that may be missed by Gram staining altogether, for example in the case of co-infections. These include a broad Pan Gram-Negative assay as well as a Pan Candida assay, which is designed to detect four of the most prevalent Candida species: Candida albicans, Candida glabrata, Candida krusei and Candida parapsilosis. The detection and identification of specific bacterial and fungal nucleic acids from individuals {3}------------------------------------------------ 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 the ePlex BCID-GP Panel 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 the ePlex BCID-GP Panel 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 ePlex BCID-GP Panel and for susceptibility testing. differentiation of mixed growth and association of antimicrobial resistance marker genes to a specific organism) and clinical presentation must be taken into consideration in the final diagnosis of blood stream infection. | 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." {4}------------------------------------------------ #### 510(k) Summary Summary of Safety and Effectiveness #### Submitter Information GenMark Diagnostics, Incorporated Submitter: 5964 La Place Court Carlsbad, CA 92008 - Manufacturer: GenMark Diagnostics, Incorporated 5964 La Place Court Carlsbad, CA 92008 Establishment Registration Number: 3008632402 | Contact: | Alan Maderazo, Ph.D., RAC
Vice President, Quality, Regulatory and Clinical Affairs | |--------------------|---------------------------------------------------------------------------------------| | Phone: | 760-448-4308 | | Fax: | 760-683-6961 | | E-mail: | Al.Maderazo@genmarkdx.com | | Alternate Contact: | Beth Stofka
Sr. Regulatory Affairs Specialist | | Phone: | 760-579-4778 | | Fax: | 760-683-6961 | | E-mail: | Beth.Stofka@genmarkdx.com | | Date Prepared: | June 22, 2018 | #### Name of Device and Classification | Product Name: | ePlex® Blood Culture Identification Gram-Positive (BCID-GP) Panel | |------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------| | Device Classification: | 866.3980, Multiplex nucleic acid assay for identification of
microorganisms and resistance markers from positive blood cultures,
Class II | | Product Code(s): | PAM, PEN, PEO | {5}------------------------------------------------ #### Predicate Device Predicate: FilmArray Blood Culture Identification Panel; BioFire Diagnostics; K130914 #### Device Description The ePlex Blood Culture Identification Gram-Positive (BCID-GP) Panel is based on the principles of competitive nucleic acid hybridization using a sandwich assay format, wherein a single-stranded target binds concurrently to a sequence-specific solution-phase signal probe and a solid-phase electrode-bound capture probe. The test employs nucleic acid extraction, target amplification via polymerase chain reaction (PCR) or reverse transcription PCR (RT-PCR) and hybridization of target DNA. In the process, the double-stranded PCR amplicons are digested with exonuclease to generate single-stranded DNA suitable for hybridization. Nucleic acid extraction from biological samples occurs within the cartridge via cell lysis, nucleic acid capture onto magnetic beads, and release for amplification. The nucleic acid extraction is processed through microfluidic liquid handling. Once the nucleic acid targets are captured and inhibitors are washed away, the magnetic particles are delivered to the electrowetting environment on the printed circuit board (PCB) and the targets are eluted from the particles and amplified. During hybridization, the single-stranded target DNA binds to a complementary, single-stranded capture probe immobilized on the working gold electrode surface. Single-stranded signal probes (labeled with electrochemically active ferrocenes) bind to specific target sequence / region adjacent to the capture probe. Simultaneous hybridization of target to signal probes and capture probe is detected by alternating current voltammetry (ACV). Each working electrode on the array contains specific capture probes, and sequential analysis of each electrode allows detection of multiple analyte targets. {6}------------------------------------------------ #### Intended Use/Indications for Use The GenMark ePlex® Blood Culture Identification Gram-Positive (BCID-GP) Panel is a qualitative nucleic acid multiplex in vitro diagnostic test intended for use on GenMark's ePlex Instrument for simultaneous qualitative detection and identification of multiple potentially pathogenic gram-positive bacterial organisms and select determinants associated with antimicrobial resistance in positive blood culture. In addition, the ePlex BCID-GP Panel is capable of detecting a wide variety of gram-negative bacteria (Pan Gram-Negative assay) and several Candida species (Pan Candida assay). The ePlex BCID-GP Panel is performed directly on blood culture samples identified as positive by a continuous monitoring blood culture system and which contain gram-positive organism. The following bacterial organisms and genes associated with antibiotic resistance are identified using the ePlex BCID-GP Panel: Bacillus cereus group, Bacillus subtilis group, Corynebacterium, Cutibacterium acnes (Propionibacterium acnes), Enterococcus, Enterococcus faecalis, Enterococcus faecium, Lactobacillus, Listeria monocytogenes, Micrococcus, Staphylococcus, Staphylococcus aureus, Staphylococcus epidermidis, Staphylococcus lugdunensis, Streptococcus, Streptococcus agalactiae (GBS), Streptococcus anginosus group, Streptococcus pneumoniae, Streptococcus pyogenes (GAS), mecA, mecC, vanA and vanB. The ePlex BCID-GP Panel contains assays for the detection of genetic determinants associated with resistance to methicillin (mecA and mecC) and vancomycin (vanA and vanB) to aid in the identification of potentially antimicrobial resistant organisms in positive blood culture samples. The antimicrobial resistance gene detected may or may not be associated with the agent responsible for disease. The ePlex BCID-GP Panel also contains targets designed to detect a broad range of organisms with a potentially misleading Gram stain result or organisms that may be missed by Gram staining altogether, for example in the case of co-infections. These include a broad Pan Gram-Negative assay as well as a Pan Candida assay, which is designed to detect four of the most prevalent Candida species: Candida albicans, Candida glabrata, Candida krusei and Candida parapsilosis. {7}------------------------------------------------ The detection and identification of specific bacterial and 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 the ePlex BCID-GP Panel 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 the ePlex BCID-GP Panel 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 ePlex BCID-GP Panel and for susceptibility testing. differentiation of mixed growth and association of antimicrobial resistance marker genes to a specific organism) and clinical presentation must be taken into consideration in the final diagnosis of blood stream infection. #### Summary of Technological Characteristics of the Device Compared to the Predicate Device The GenMark ePlex Blood Culture Identification Gram-Positive (BCID-GP) Panel ("Subject Device") and the legally marketed device, FilmArray Blood Culture Identification Gram-Positive Panel, K130914, ("Predicate Device") are described below: | Characteristic | Subject Device | Predicate Device | |-------------------------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------| | Product Name | ePlex BCID-GP Panel | FilmArray BCID Panel | | Manufacturer | GenMark Diagnostics, Inc. | BioFire Diagnostics, Inc. | | Organisms
Detected | Bacillus cereus group Bacillus subtilis group Corynebacterium Cutibacterium acnes (P. acnes) Enterococcus Enterococcus facealis Enterococcus faecium Lactobacillus Listeria Listeria monocytogenes Micrococcus Staphylococcus Staphylococcus aureus Staphylococcus epidermidis | Enterococci, Listeria monocytogenes,
commonly encountered Staphylococci
(including specific differentiation of
Staphylococcus aureus), commonly
encountered Streptococci (with
specific differentiation of
Streptococcus agalactiae,
Streptococcus pneumoniae, and
Streptococcus pyogenes),
Acinetobacter baumannii, commonly
encountered Enterobacteriaceae
(including specific differentiation of
the Enterobacter cloacae complex,
Escherichia coli, Klebsiella oxytoca, | | Characteristic | Subject Device | Predicate Device | | | Staphylococcus lugdunensis Streptococcus Streptococcus agalactiae (GBS) Streptococcus anginosus group Streptococcus pneumonia Streptococcus pyogenes (GAS) Pan Gram-Negative Pan Candida | Klebsiella pneumoniae, Proteus, and
Serratia marcescens), Haemophilus
influenzae, Neisseria meningitidis
(encapsulated), Pseudomonas
aeruginosa, Candida albicans,
Candida glabrata, Candida krusei,
Candida parapsilosis, and Candida
tropicalis. | | Resistance Genes
Detected | Genetic determinants of resistance to
methicillin ( mecA and mecC ) and
vancomycin ( vanA and vanB ) | Genetic determinants of resistance to
methicillin ( mecA ), vancomycin
( vanA and vanB ), and carbapenems
( bla KPC) | | Indication for
Use | The GenMark BCID-GP panel is
indicated as an aid in the diagnosis of
specific agents of bacteremia. The use
of additional laboratory testing (e.g.
sub-culturing of positive blood cultures
for identification of organisms not
detected by BCID-GP Panel and for
susceptibility testing, differentiation of
mixed growth, and association of
antimicrobial resistance marker genes to
a specific organism) and clinical
presentation must be taken into
consideration in the final diagnosis of
blood stream infection. | FilmArray BCID is indicated as an aid
in the diagnosis of specific agents of
bacteremia and fungemia and results
should be used in conjunction with
other clinical and laboratory findings. | | Specimen Type | Gram-Positive Blood Culture | Gram-Positive & Gram-Negative
Blood Culture | | Chemistry | Reagents on cartridge include: sample
lysis and nucleic acid extraction, PCR
amplification and hybridization-based
electrochemical detection reagents. | The FilmArray BCID pouch contains
freeze-dried reagents to perform
nucleic acid purification and nested,
multiplex PCR with DNA melt
analysis. | | Hardware | GenMark ePlex Instrument & Single
Use Cartridge | FilmArray Instrument and assay pouch | | Software
Interface
Result Reporting | GenMark ePlex System Software GenMark ePlex BCID-GP Panel
Software | The FilmArray Software automatically
interprets the results of each DNA
melt curve analysis and combines the
data with the results of the internal
pouch controls to provide a test result
for each organism and antimicrobial
resistance gene on the panel. | {8}------------------------------------------------ Analysis of the similarities and differences indicate that the devices are substantially equivalent in their intended uses/indications for use, and are generally the same regarding user process, ease {9}------------------------------------------------ of use and general operator protocol. Comparison of technological similarities and differences between the proposed device and the predicate do not raise new or different questions of safety and effectiveness, and therefore render the proposed device as substantially equivalent to the predicate device. #### Summary of Performance Data #### EXPECTED VALUES A prospective, multicenter clinical study was conducted to evaluate the clinical performance of the ePlex BCID-GP Panel in positive blood culture samples. A total of 711 samples were prospectively collected at 7 clinical sites in 2 phases from patients of all ages and genders. In the first phase from June 2014 through July 2016, 399 samples were prospectively collected and frozen; from January through February 2018, 312 samples were prospectively collected and tested fresh (never frozen). The expected values of individual analytes based on the ePlex BCID-GP Panel results in prospective samples are summarized by age group and by site in Table 1 and Table 2, respectively. {10}------------------------------------------------ ## Table 1: Expected Value by Age Group (Prospective Samples) | Target | All Ages
(N=711) | Age <1
(N=27) | Age 1-17
(N=42) | Age 18-44
(N=121) | Age 45-64
(N=2500) | Age 65-84
(N=217) | Age 85+
(N=54) | Target | All Sites
(N=711) | Site 1
(N=161) | Site 2
(N=58) | Site 3
(N=164) | Site 4
(N=145) | Site 5
(N=77) | Site 6
(N=33) | Site 7
(N=73) | |----------------------------------------------------------|---------------------|------------------|--------------------|----------------------|-----------------------|----------------------|-------------------|----------------------------------------------------------|----------------------|-------------------|------------------|-------------------|-------------------|------------------|------------------|------------------| | Bacillus cereus group | 5 (0.7) | 0 (0.0) | 0 (0.0) | 3 (2.5) | 2 (0.8) | 0 (0.0) | 0 (0.0) | Bacillus cereus group | 5 (0.7) | 3 (1.9) | 1 (1.7) | 1 (0.6) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) | | Bacillus subtilis group | 2 (0.3) | 0 (0.0) | 0 (0.0) | 1 (0.8) | 0 (0.0) | 0 (0.0) | 1 (1.9) | Bacillus subtilis group | 2 (0.3) | 0 (0.0) | 1 (1.7) | 0 (0.0) | 0 (0.0) | 1 (1.3) | 0 (0.0) | 0 (0.0) | | Corynebacterium | 14 (2.0) | 1 (3.7) | 0 (0.0) | 4 (3.3) | 5 (2.0) | 4 (1.8) | 0 (0.0) | Corynebacterium | 14 (2.0) | 2 (1.2) | 2 (3.4) | 0 (0.0) | 6 (4.1) | 2 (2.6) | 0 (0.0) | 2 (2.7) | | Cutibacterium acnes (P. acnes) | 8 (1.1) | 0 (0.0) | 0 (0.0) | 3 (2.5) | 2 (0.8) | 3 (1.4) | 0 (0.0) | Cutibacterium acnes (P. acnes) | 8 (1.1) | 1 (0.6) | 0 (0.0) | 1 (0.6) | 2 (1.4) | 0 (0.0) | 0 (0.0) | 4 (5.5) | | Enterococcus | 62 (8.7) | 0 (0.0) | 6 (14.3) | 8 (6.6) | 20 (8.0) | 24 (11.1) | 4 (7.4) | Enterococcus | 62 (8.7) | 20 (12.4) | 7 (12.1) | 15 (9.1) | 9 (6.2) | 10 (13.0) | 1 (3.0) | 0 (0.0) | | Enterococcus faecalis | 50 (7.0) | 0 (0.0) | 6 (14.3) | 6 (5.0) | 15 (6.0) | 20 (9.2) | 3 (5.6) | Enterococcus faecalis | 50 (7.0) | 14 (8.7) | 6 (10.3) | 13 (7.9) | 8 (5.5) | 8 (10.4) | 1 (3.0) | 0 (0.0) | | Enterococcus faecium | 12 (1.7) | 0 (0.0) | 0 (0.0) | 1 (0.8) | 6 (2.4) | 5 (2.3) | 0 (0.0) | Enterococcus faecium | 12 (1.7) | 6 (3.7) | 1 (1.7) | 1 (0.6) | 2 (1.4) | 2 (2.6) | 0 (0.0) | 0 (0.0) | | Lactobacillus | 5 (0.7) | 0 (0.0) | 0 (0.0) | 2 (1.7) | 1 (0.4) | 1 (0.5) | 1 (1.9) | Lactobacillus | 5 (0.7) | 1 (0.6) | 1 (1.7) | 2 (1.2) | 0 (0.0) | 1 (1.3) | 0 (0.0) | 0 (0.0) | | Listeria | 1 (0.1) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 1 (0.5) | 0 (0.0) | Listeria | 1 (0.1) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 1 (0.7) | 0 (0.0) | 0 (0.0) | 0 (0.0) | | Listeria monocytogenes | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) | Listeria monocytogenes | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) | | Micrococcus | 19 (2.7) | 0 (0.0) | 3 (7.1) | 2 (1.7) | 8 (3.2) | 5 (2.3) | 1 (1.9) | Micrococcus | 19 (2.7) | 2 (1.2) | 2 (3.4) | 5 (3.0) | 6 (4.1) | 0 (0.0) | 0 (0.0) | 4 (5.5) | | Staphylococcus | 452 (63.6) | 23 (85.2) | 23 (54.8) | 78 (64.5) | 154 (61.6) | 139 (64.1) | 35 (64.8) | Staphylococcus | 452 (63.6) | 106 (65.8) | 27 (46.6) | 109 (66.5) | 98 (67.6) | 52 (67.5) | 24 (72.7) | 36 (49.3) | | Staphylococcus aureus | 162 (22.8) | 8 (29.6) | 4 (9.5) | 37 (30.6) | 69 (27.6) | 38 (17.5) | 6 (11.1) | Staphylococcus aureus | 162 (22.8) | 36 (22.4) | 7 (12.1) | 56 (34.1) | 27 (18.6) | 18 (23.4) | 6 (18.2) | 12 (16.4) | | Staphylococcus epidermidis | 182 (25.6) | 10 (37.0) | 11 (26.2) | 26 (21.5) | 54 (21.6) | 62 (28.6) | 19 (35.2) | Staphylococcus epidermidis | 182 (25.6) | 41 (25.5) | 14 (24.1) | 34 (20.7) | 44 (30.3) | 23 (29.9) | 13 (39.4) | 13 (17.8) | | Staphylococcus lugdunensis | 5 (0.7) | 1 (3.7) | 0 (0.0) | 0 (0.0) | 3 (1.2) | 0 (0.0) | 1 (1.9) | Staphylococcus lugdunensis | 5 (0.7) | 0 (0.0) | 0 (0.0) | 2 (1.2) | 2 (1.4) | 0 (0.0) | 0 (0.0) | 1 (1.4) | | Streptococcus | 110 (15.5) | 5 (18.5) | 9 (21.4) | 16 (13.2) | 40 (16.0) | 31 (14.3) | 9 (16.7) | Streptococcus | 110 (15.5) | 18 (11.2) | 9 (15.5) | 28 (17.1) | 20 (13.8) | 11 (14.3) | 5 (15.2) | 19 (26.0) | | Streptococcus agalactiae | 12 (1.7) | 1 (3.7) | 0 (0.0) | 1 (0.8) | 5 (2.0) | 5 (2.3) | 0 (0.0) | Streptococcus agalactiae | 12 (1.7) | 2 (1.2) | 0 (0.0) | 2 (1.2) | 2 (1.4) | 2 (2.6) | 2 (6.1) | 2 (2.7) | | Streptococcus anginosus group | 10 (1.4) | 0 (0.0) | 0 (0.0) | 2 (1.7) | 3 (1.2) | 3 (1.4) | 2 (3.7) | Streptococcus anginosus group | 10 (1.4) | 2 (1.2) | 0 (0.0) | 6 (3.7) | 0 (0.0) | 2 (2.6) | 0 (0.0) | 0 (0.0) | | Streptococcus pneumoniae | 28 (3.9) | 2 (7.4) | 2 (4.8) | 3 (2.5) | 12 (4.8) | 8 (3.7) | 1 (1.9) | Streptococcus pneumoniae | 28 (3.9) | 3 (1.9) | 5 (8.6) | 5 (3.0) | 4 (2.8) | 1 (1.3) | 0 (0.0) | 10 (13.7) | | Streptococcus pyogenes | 8 (1.1) | 0 (0.0) | 0 (0.0) | 1 (0.8) | 5 (2.0) | 2 (0.9) | 0 (0.0) | Streptococcus pyogenes | 8 (1.1) | 1 (0.6) | 0 (0.0) | 3 (1.8) | 1 (0.7) | 1 (1.3) | 0 (0.0) | 2 (2.7) | | Pan Candida | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) | Pan Candida | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) | | Pan Gram-Negative | 25 (3.5) | 0 (0.0) | 4 (9.5) | 4 (3.3) | 10 (4.0) | 6 (2.8) | 1 (1.9) | Pan Gram-Negative | 25 (3.5) | 9 (5.6) | 4 (6.9) | 3 (1.8) | 2 (1.4) | 5 (6.5) | 1 (3.0) | 1 (1.4) | | mecA (Staphylococcus) | 261 (36.7) | 14 (51.9) | 10 (23.8) | 41 (33.9) | 83 (33.2) | 94 (43.3) | 19 (35.2) | mecA (Staphylococcus) | 261 (36.7) | 69 (42.9) | 17 (29.3) | 68 (41.5) | 55 (37.9) | 25 (32.5) | 13 (39.4) | 14 (19.2) | | mecA (S. aureus) | 86 (12.1) | 4 (14.8) | 1 (2.4) | 17 (14.0) | 35 (14.0) | 26 (12.0) | 3 (5.6) | mecA (S. aureus) | 86 (12.1) | 19 (11.8) | 5 (8.6) | 28 (17.1) | 19 (13.1) | 7 (9.1) | 3 (9.1) | 5 (6.8) | | mecA (S. epidermidis) | 137 (19.3) | 8 (29.6) | 9 (21.4) | 19 (15.7) | 38 (15.2) | 48 (22.1) | 15 (27.8) | mecA (S. epidermidis) | 137 (19.3) | 36 (22.4) | 10 (17.2) | 31 (18.9) | 29 (20.0) | 17 (22.1) | 8 (24.2) | 6 (8.2) | | mecA (S. lugdunensis) | 1 (0.1) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 1 (0.4) | 0 (0.0) | 0 (0.0) | mecA (S. lugdunensis) | 1 (0.1) | 0 (0.0) | 0 (0.0) | 1 (0.6) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) | | mecA (CoNS excluding S.
epidermidis / S. lugdunensis) | 40 (5.6) | 2 (7.4) | 0 (0.0) | 6 (5.0) | 10 (4.0) | 20 (9.2) | 2 (3.7) | mecA (CoNS excluding S.
epidermidis / S. lugdunensis) | 40 (5.6) | 15 (9.3) | 2 (3.4) | 9 (5.5) | 7 (4.8) | 2 (2.6) | 2 (6.1) | 3 (4.1) | | mecC (Staphylococcus) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) | mecC (Staphylococcus) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) | | vanA (Enterococcus) | 9 (1.3) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 6 (2.4) | 3 (1.4) | 0 (0.0) | vanA (Enterococcus) | 9 (1.3) | 6 (3.7) | 0 (0.0) | 1 (0.6) | 1 (0.7) | 1 (1.3) | 0 (0.0) | 0 (0.0) | | vanA (E. faecalis) | 1 (0.1) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 1 (0.4) | 0 (0.0) | 0 (0.0) | vanA (E. faecalis) | 1 (0.1) | 1 (0.6) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) | | vanA (E. faecium) | 8 (1.1) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 5 (2.0) | 3 (1.4) | 0 (0.0) | vanA (E. faecium) | 8 (1.1) | 5 (3.1) | 0 (0.0) | 1 (0.6) | 1 (0.7) | 1 (1.3) | 0 (0.0) | 0 (0.0) | | vanB (Enterococcus) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) | vanB (Enterococcus) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) | {11}------------------------------------------------ ## Table 2: Expected Value by Collection Site (Prospective Samples) {12}------------------------------------------------ #### PERFORMANCE CHARACTERISTICS #### Clinical Performance Samples with final, valid ePlex BCID-GP Panel test results and a valid comparator result were evaluable and included in summaries and analyses of demographics, expected values (positivity rate), and performance characteristics. Evaluable samples included 312 prospective fresh and 399 prospective frozen samples as well as 586 retrospective samples and 565 contrived samples. #### Comparator Method The performance of the ePlex BCID-GP Panel was compared to standard laboratory procedures, including traditional and automated culture, MALDI-TOF IVD, and microbiological and biochemical techniques for organism identification for samples with Corynebacterium, Staphylococcus epidermidis, Staphylococcus hominis, or Candida parapsilosis identified by standard laboratory procedures were confirmed using analytically validated PCR assays followed by bi-directional sequencing or 16S sequencing. For antibiotic resistance genes, the ePlex BCID-GP Panel was compared to analytically validated qPCR amplification assays followed by bi-directional sequencing in samples with an associated organism identified (i.e., Staphylococcus, Enterococcus). The comparator method(s) results were used to determine the Detected / Not Detected status for each target organism on the ePlex BCID-GP Panel. The comparator methods for each target are summarized in Table 3. {13}------------------------------------------------ #### Table 3: Comparator Method(s) by ePlex BCID-GP Panel Target | Target | Comparator Method | |-----------------------------------------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------| | Bacillus cereus group | | | Bacillus subtilis group | | | Cutibacterium acnes (Propionibacterium acnes) | | | Enterococcus | | | Enterococcus faecalis | | | Enterococcus faecium | | | Lactobacillus | | | Listeria | | | Listeria monocytogenes | | | Micrococcus | Standard laboratory procedures for organism identification. | | Staphylococcus | | | Staphylococcus aureus | | | Staphylococcus lugdunensis | | | Streptococcus | | | Streptococcus agalactiae | | | Streptococcus anginosus group | | | Streptococcus pneumoniae | | | Streptococcus pyogenes | | | Pan Gram-Negative | | | Corynebacterium | Standard laboratory procedures for organism ID.
PCR/sequencing and 16S sequencing to confirm (or
identify Coryneform) or exclude Corynebacterium species
not included in this panel target* | | Staphylococcus epidermidis | Standard laboratory procedures for organism ID.
PCR/sequencing to confirm S. epidermidis, S. hominis | | Pan Candida | Standard laboratory procedures for organism ID.
PCR/sequencing to confirm C. parapsilosis or identify
C. metapsilosis, C. orthopsilosis | | mecA | qPCR/sequencing in samples with Staphylococcus
identified | | mecC | | | vanA | qPCR/sequencing in samples with Enterococcus identified | The Corynebacterium assay is not designed to detect the following Corynebacterium species: C. amycolatum, C. argentoratense, C. bovis, C. durum, C. glucuronolyticum, C. macginleyi, C. propinquum, C. riegelii, and C. sundsvallense #### Demographics of Clinical Samples Clinical performance was evaluated in positive blood culture samples prospectively and retrospectively collected. Prospective samples were collected at 7 clinical sites in 2 phases. From June 2014 through July 2016, 400 samples were prospectively collected and frozen; from January through February 2018, 319 samples were prospectively collected and tested fresh (never frozen) for a total of 719 samples across the 2 phases. 8 of these samples were withdrawn; {14}------------------------------------------------ 5 due to the sample coming from a patient already enrolled; 1 was collected outside of the required timeframe; 1 was not viable upon subculture and 1 was from an autopsy. Samples with final, valid ePlex BCID-GP Panel results and a valid comparator result were considered evaluable. Of the 711 prospectively-collected samples eligible for testing, all 711 were evaluable. Demographic information for prospectively-collected samples is described in Table 4. Subjects enrolled in this study were from a diverse demographic distribution and represent the intended patient population. To supplement the number of positives for low prevalence targets in the prospective collection, 586 samples were collected retrospectively, and all 586 were evaluable. Demographic information for retrospectively-collected samples is described in Table 5. | | All Sites
N = 711 | Site 1
N = 161 | Site 2
N = 58 | Site 3
N = 164 | Site 4
N = 145 | Site 5
N = 77 | Site 6
N = 33 | Site 7
N = 73 | |-----------|----------------------|-------------------|------------------|-------------------|-------------------|------------------|------------------|------------------| | Sex | | | | | | | | | | Male | 377 (53.0) | 93 (57.8) | 28 (48.3) | 91 (55.5) | 66 (45.5) | 42 (54.5) | 17 (51.5) | 40 (54.8) | | Female | 334 (47.0) | 68 (42.2) | 30 (51.7) | 73 (44.5) | 79 (54.5) | 35 (45.5) | 16 (48.5) | 33 (45.2) | | Age | | | | | | | | | | <1 yr | 27 (3.8) | 3 (1.9) | 0 (0.0) | 8 (4.9) | 10 (6.9) | 4 (5.2) | 2 (6.1) | 0 (0.0) | | 1-17 yrs | 42 (5.9) | 8 (5.0) | 2 (3.4) | 11 (6.7) | 10 (6.9) | 7 (9.1) | 2 (6.1) | 2 (2.7) | | 18-44 yrs | 121 (17) | 32 (19.9) | 9 (15.5) | 24 (14.6) | 24 (16.6) | 13 (16.9) | 4 (12.1) | 15 (20.5) | | 45-64 yrs | 250 (35.2) | 66 (41.0) | 18 (31.0) | 67 (40.9) | 36 (24.8) | 25 (32.5) | 11 (33.3) | 27 (37.0) | | 65-84 yrs | 217 (30.5) | 44 (27.3) | 20 (34.5) | 41 (25.0) | 51 (35.2) | 23 (29.9) | 13 (39.4) | 25 (34.2) | | 85+ yrs | 54 (7.6) | 8 (5.0) | 9 (15.5) | 13 (7.9) | 14 (9.7) | 5 (6.5) | 1 (3.0) | 4 (5.5) | Table 4: Demographic Data for Clinical Samples by Collection Site (Prospective Collection) {15}------------------------------------------------ | | All Sites
N = 586 | Site 1
N = 80 | Site 2
N = 98 | Site 3
N = 51 | Site 4
N = 43 | Site 5
N = 3 | Site 6
N = 61 | Site 7
N = 85 | Site 8
N = 25 | Site 9
N = 46 | Site 10
N = 94 | |-----------|----------------------|------------------|------------------|------------------|------------------|-----------------|------------------|------------------|------------------|------------------|-------------------| | Sex | | | | | | | | | | | | | Male | 317 (54.1) | 39 (48.8) | 59 (60.2) | 24 (47.1) | 20 (46.5) | 1 (33.3) | 36 (59.0) | 45 (52.9) | 17 (68.0) | 28 (60.9) | 48 (51.1) | | Female | 269 (45.9) | 41 (51.3) | 39 (39.8) | 27 (52.9) | 23 (53.5) | 2 (66.7) | 25 (41.0) | 40 (47.1) | 8 (32.0) | 18 (39.1) | 46 (48.9) | | Age | | | | | | | | | | | | | <1 yr | 11 (1.9) | 1 (1.3) | 2 (2) | 0 (0) | 3 (7) | 0 (0) | 1 (1.6) | 0 (0) | 0 (0) | 1 (2.2) | 3 (3.2) | | 1-17 yrs | 17 (2.9) | 6 (7.5) | 1 (1) | 0 (0) | 4 (9.3) | 0 (0) | 0 (0) | 0 (0) | 1 (4) | 1 (2.2) | 4 (4.3) | | 18-44 yrs | 104 (17.7) | 14 (17.5) | 13 (13.3) | 5 (9.8) | 9 (20.9) | 0 (0) | 15 (24.6) | 11 (12.9) | 7 (28) | 5 (10.9) | 25 (26.6) | | 45-64 yrs | 193 (32.9) | 25 (31.3) | 33 (33.7) | 17 (33.3) | 15 (34.9) | 1 (33.3) | 21 (34.4) | 30 (35.3) | 10 (40) | 12 (26.1) | 29 (30.9) | | 65-84 yrs | 209 (35.7) | 26 (32.5) | 42 (42.9) | 22 (43.1) | 9 (20.9) | 0 (0) | 20 (32.8) | 35 (41.2) | 7 (28) | 18 (39.1) | 30 (31.9) | | 85+ yrs | 50 (8.5) | 8 (10) | 7 (7.1) | 7 (13.7) | 3 (7) | 2 (66.7) | 4 (6.6) | 7 (8.2) | 0 (0) | 9 (19.6) | 3 (3.2) | | Unknown | 2 (0.3) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 2 (2.4) | 0 (0) | 0 (0) | 0 (0) | | Table 5: Demographic Data for Clinical Samples by Collection Site (Retrospective Collection) | | | | | |----------------------------------------------------------------------------------------------|--|--|--|--| | | | | | | #### Clinical Performance Sensitivity or positive percent agreement (PPA) was calculated by dividing the number of true positive (TP) results by the sum of TP and false negative (FN) results, while specificity or negative percent agreement (NPA) was calculated by dividing the number of true negative (TN) results by the sum of TN and false positive (FP) result being defined as a sample where the detected ePlex BCID-GP Panel result matched the detected comparator method result, while a TN result was one where a negative ePlex BCID-GP Panel result matched a negative comparator method result. The two-sided 95% confidence interval was also calculated. A total of 711 prospectively-collected samples (312 tested fresh and 399 tested after previously frozen) and 586 retrospectively collected samples as well as 565 contrived samples were evaluated for the ePlex BCID-GP Panel targets. Contrived samples were prepared by spiking an isolate into a blood culture bottle and growing until flagged positive by a continuously monitoring blood culture system. Samples were removed from the system within 8 hours of positivity and stored frozen until the time of testing. PPA and NPA results are summarized by target in Tables 6-30 and the strains used to contrive samples are summarized in Table 31. {16}------------------------------------------------ | | | Sensitivity/PPA | | Specificity/NPA | | |-----------------------|---------------------------|-----------------|------------------|-----------------|----------------| | Target | Sample Type | TP/TP+FN | % (95% CI) | TN/TN+FP | % (95% CI) | | Bacillus cereus group | Prospective (Fresh) | 2/2 | 100 (34.2-100) | 310/310 | 100 (98.8-100) | | | Prospective (Frozen) | 3/3 | 100 (43.9-100) | 396/396 | 100 (99.0-100) | | | Prospective (All) | 5/5 | 100 (56.6-100) | 706/706 | 100 (99.5-100) | | | Retrospective | 6/7 | 85.7 (48.7-97.4) | 579/579 | 100 (99.3-100) | | | Prospective/Retrospective | 11/12 | 91.7 (64.6-98.5) | 1765/1765 | 100 (99.8-100) | | | Contrived | 46/46 | 100 (92.3-100) | 519/519 | 100 (99.3-100) | | | Overall | 57/58 | 98.3 (90.9-99.7) | 2284/2284 | 100 (99.8-100) | #### Table 6: Clinical Performance for Bacillus cereus group CI= Confidence Interval #### Table 7: Clinical Performance for Bacillus subtilis group | Target | Sample Type | Sensitivity/PPA | | Specificity/NPA | | |-------------------------|---------------------------|-----------------|----------------|-----------------|----------------| | | | TP/TP+FN | % (95% CI) | TN/TN+FP | % (95% CI) | | Bacillus subtilis group | Prospective (Fresh) | 2/2 | 100 (34.2-100) | 309/309 | 100 (98.8-100) | | | Prospective (Frozen) | 0/0 | --- | 399/399 | 100 (99.0-100) | | | Prospective (All) | 2/2 | 100 (34.2-100) | 708/708 | 100 (99.5-100) | | | Retrospective | 0/0 | --- | 586/586 | 100 (99.3-100) | | | Prospective/Retrospective | 2/2 | 100 (34.2-100) | 1294/1294 | 100 (99.7-100) | | | Contrived | 50/50 | 100 (92.9-100) | 515/515 | 100 (99.3-100) | | | Overall | 52/52 | 100 (93.1-100) | 1809/1809 | 100 (99.8-100) | #### Table 8: Clinical Performance for Corynebacterium | Target | Sample Type | Sensitivity/PPA | | Specificity/NPA | | |-----------------|---------------------------|-----------------|------------------|-----------------|------------------| | | | TP/TP+FN | % (95% CI) | TN/TN+FP | % (95% CI) | | Corynebacterium | Prospective (Fresh) | 5/7 | 71.4 (35.9-91.8) | 304/305 | 99.7 (98.2-99.9) | | | Prospective (Frozen) | 8/12 | 66.7 (39.1-86.2) | 387/387 | 100 (99.0-100) | | | Prospective (All) | 13/19 | 68.4 (46.0-84.6) | 691/692 | 99.9 (99.2-100) | | | Retrospective | 27/32 | 84.4 (68.2-93.1) | 553/554 | 99.8 (99.0-100) | | | Prospective/Retrospective | 40/51A | 78.4 (65.4-87.5) | 1244/1246B | 99.8 (99.4-100) | | | Contrived | 20/20 | 100 (83.9-100) | 545/545 | 100 (99.3-100) | | | Overall | 60/71 | 84.5 (74.3-91.1) | 1789/1791 | 99.9 (99.6-100) | A. Corynebacterium was not detected in 4 of the false negative samples using but 16S sequencing instead detected Staphylococus pettenkoferi, Macrococcus caseolyticus, Lactobacterium and Cutibacterium acnes, which were not dentified by standard laboratory procedures. B. Corynebacterium was detected in 2/2 false positive samples using PCR/sequencing. {17}------------------------------------------------ | Target | Sample Type | Sensitivity/PPA | | Specificity/NPA | | |---------------------|---------------------------|-----------------|------------------|-----------------|------------------| | | | TP/TP+FN | % (95% CI) | TN/TN+FP | % (95% CI) | | Cutibacterium acnes | Prospective (Fresh) | 4/5 | 80.0 (37.6-96.4) | 306/307 | 99.7 (98.2-99.9) | | | Prospective (Frozen) | 2/2 | 100 (34.2-100) | 396/397 | 99.7 (98.6-100) | | | Prospective (All) | 6/7 | 85.7 (48.7-97.4) | 702/704 | 99.7 (99.0-99.9) | | | Retrospective | 12/13 | 92.3 (66.7-98.6) | 573/573 | 100 (99.3-100) | | | Prospective/Retrospective | 18/20 | 90.0 (69.9-97.2) | 1275/1277A | 99.8 (99.4-100) | | | Contrived | 25/26 | 96.2 (81.1-99.3) | 539/539 | 100 (99.3-100) | | | Overall | 43/46 | 93.5 (82.5-97.8) | 1814/1816 | 99.9 (99.6-100) | #### Table 9: Clinical Performance for Cutibacterium acnes A. Cutibacterium acnes was detected in 1/2 false positive samples using PCR/sequencing. #### Table 10: Clinical Performance for Enterococcus | Target | Sample Type | Sensitivity/PPA | | Specificity/NPA | | |--------------|---------------------------|-----------------|------------------|-----------------|-----------------| | | | TP/TP+FN | % (95% CI) | TN/TN+FP | % (95% CI) | | Enterococcus | Prospective (Fresh) | 25/25 | 100 (86.7-100) | 287/287 | 100 (98.7-100) | | | Prospective (Frozen) | 36/36 | 100 (90.4-100) | 362/363 | 99.7 (98.5-100) | | | Prospective (All) | 61/61 | 100 (94.1-100) | 649/650 | 99.8 (99.1-100) | | | Retrospective | 139/147 | 94.6 (89.6-97.2) | 439/439 | 100 (99.1-100) | | | Prospective/Retrospective | 200/208A | 96.2 (92.6-98.0) | 1088/1089B | 99.9 (99.5-100) | | | Contrived | 126/126 | 100 (97.0-100) | 439/439 | 100 (99.1-100) | | | Overall | 326/334 | 97.6 (95.3-98.8) | 1527/1528 | 99.9 (99.6-100) | A. Enterococcus was not detected in 1 false negative sample, but PCR/sequencing instead detected Lactis, which was not identified by standard laboratory procedures. B. Enterococcus was detected in 1/1 false positive samples using PCR/sequencing. #### Table 11: Clinical Performance for Enterococcus faecalis | Target | Sample Type | Sensitivity/PPA | | Specificity/NPA | | |-----------------------|---------------------------|-----------------|------------------|-----------------|----------------| | | | TP/TP+FN | % (95% CI) | TN/TN+FP | % (95% CI) | | Enterococcus faecalis | Prospective (Fresh) | 21/21 | 100 (84.5-100) | 291/291 | 100 (98.7-100) | | | Prospective (Frozen) | 28/28 | 100 (87.9-100) | 370/370 | 100 (99.0-100) | | | Prospective (All) | 49/49 | 100 (92.7-100) | 661/661 | 100 (99.4-100) | | | Retrospective | 82/90 | 91.1 (83.4-95.4) | 496/496 | 100 (99.2-100) | | | Prospective/Retrospective | 131/139^ | 94.2 (89.1-97.1) | 1157/1157 | 100 (99.7-100) | | | Contrived | 52/52 | 100 (93.1-100) | 513/513 | 100 (99.3-100) | | | Overall | 183/191 | 95.8 (92.0-97.9) | 1670/1670 | 100 (99.8-100) | A. Enterococcus faecalis was not detected in 4 false negative samples, but PCR/sequencing instead detected Enterococcus faccium (3) and Lactococcus lactis (1), which were not identified by standard laboratory procedures. Confidential {18}------------------------------------------------ | Target | Sample Type | Sensitivity/PPA | | Specificity/NPA | | |----------------------|---------------------------|-----------------|------------------|-----------------|------------------| | | | TP/TP+FN | % (95% CI) | TN/TN+FP | % (95% CI) | | Enterococcus faecium | Prospective (Fresh) | 3/3 | 100 (43.9-100) | 309/309 | 100 (98.8-100) | | | Prospective (Frozen) | 8/9 | 88.9 (56.5-98.0) | 388/389 | 99.7 (98.6-100) | | | Prospective (All) | 11/12 | 91.7 (64.6-98.5) | 697/698 | 99.9 (99.2-100) | | | Retrospective | 52/53 | 98.1 (90.1-99.7) | 526/533 | 98.7 (97.3-99.4) | | | Prospective/Retrospective | 63/65 | 96.9 (89.5-99.2) | 1223/1231A | 99.4 (98.7-99.7) | | | Contrived | 60/60 | 100 (94.0-100) | 505/505 | 100 (99.2-100) | | | Overall | 123/125 | 98.4 (94.4-99.6) | 1728/1736 | 99.5 (99.1-99.8) | ## Table 12: Clinical Performance for Enterococcus faecium A. Enterococcus faecium was detected in 5/8 false positive samples using PCR/sequencing. ## Table 13: Clinical Performance for Lactobacillus | Target | Sample Type | Sensitivity/PPA | | Specificity/NPA | | |---------------|---------------------------|-----------------|------------------|-----------------|------------------| | | | TP/TP+FN | % (95% CI) | TN/TN+FP | % (95% CI) | | Lactobacillus | Prospective (Fresh) | 2/2 | 100 (34.2-100) | 309/310 | 99.7 (98.2-99.9) | | | Prospective (Frozen) | 2/2 | 100 (34.2-100) | 397/397 | 100 (99.0-100) | | | Prospective (All) | 4/4 | 100 (51.0-100) | 706/707 | 99.9 (99.2-100) | | | Retrospective | 9/9 | 100 (70.1-100) | 576/577 | 99.8 (99.0-100) | | | Prospective/Retrospective | 13/13 | 100 (77.2-100) | 1282/1284A | 99.8 (99.4-100) | | | Contrived | 32/33 | 97.0 (84.7-99.5) | 532/532 | 100 (99.3-100) | | | Overall | 45/46 | 97.8 (88.7-99.6) | 1814/1816 | 99.9 (99.6-100) | A. Lactobacillus casei was detected in 1/2 false positive samples using PCR/sequencing. #### Table 14: Clinical Performance for Listeria | Target | Sample Type | Sensitivity/PPA | | Specificity/NPA | | |----------|---------------------------|-----------------|------------------|-----------------|-----------------| | | | TP/TP+FN | % (95% CI) | TN/TN+FP | % (95% CI) | | Listeria | Prospective (Fresh) | 0/0 | --- | 312/312 | 100 (98.8-100) | | | Prospective (Frozen) | 0/0 | --- | 398/399 | 99.7 (98.6-100) | | | Prospective (All) | 0/0 | --- | 710/711 | 99.9 (99.2-100) | | | Retrospective | 2/2 | 100 (34.2-100) | 584/584 | 100 (99.3-100) | | | Prospective/Retrospective | 2/2 | 100 (34.2-100) | 1294/1295 | 99.9 (99.6-100) | | | Contrived | 74/75 | 98.7 (92.8-99.8) | 490/490 | 100 (99.2-100) | | | Overall | 76/77 | 98.7 (93.0-99.8) | 1784/1785 | 99.9 (99.7-100) | {19}------------------------------------------------ | Target | Sample Type | Sensitivity/PPA | | Specificity/NPA | | |---------------------------|---------------------------|-----------------|----------------|-----------------|----------------| | | | TP/TP+FN | % (95% CI) | TN/TN+FP | % (95% CI) | | Listeria
monocytogenes | Prospective (Fresh) | 0/0 | -- | 312/312 | 100 (98.8-100) | | | Prospective (Frozen) | 0/0 | -- | 399/399 | 100 (99.0-100) | | | Prospective (All) | 0/0 | -- | 711/711 | 100 (99.5-100) | | | Retrospective | 2/2 | 100 (34.2-100) | 584/584 | 100 (99.3-100) | | | Prospective/Retrospective | 2/2 | 100 (34.2-100) | 1295/1295 | 100 (99.7-100) | | | Contrived | 46/46 | 100 (92.3-100) | 519/519 | 100 (99.3-100) | | | Overall | 48/48 | 100 (92.6-100) | 1814/1814 | 100 (99.8-100) | #### Table 15: Clinical Performance for Listeria monocytogenes #### Table 16: Clinical Performance for Micrococcus | Target | Sample Type | Sensitivity/PPA | | Specificity/NPA | | |-------------|-------… --- **Source:** [https://fda.innolitics.com/submissions/MI/subpart-d%E2%80%94serological-reagents/PAM/K181663](https://fda.innolitics.com/submissions/MI/subpart-d%E2%80%94serological-reagents/PAM/K181663) **Published by [Innolitics](https://innolitics.com)** — a medical-device software consultancy. We help companies design, build, and clear FDA-regulated software and AI/ML devices. If you're preparing [a 510(k)](https://innolitics.com/services/510ks/), [a De Novo](https://innolitics.com/services/regulatory/), [a SaMD](https://innolitics.com/services/end-to-end-samd/), [an AI/ML medical device](https://innolitics.com/services/medical-imaging-ai-development/), or [an FDA regulatory strategy](https://innolitics.com/services/regulatory/), [get in touch](https://innolitics.com/contact). **Cite:** Innolitics at https://innolitics.com