(85 days)
Not Found
No
The device description focuses on nucleic acid hybridization, PCR, and electrochemical detection. There is no mention of AI or ML in the intended use, device description, or performance studies.
No.
The device is an in vitro diagnostic test for the detection and identification of fungal organisms in positive blood cultures, aiding in the diagnosis of bloodstream infections, rather than directly treating or preventing disease.
Yes
The device is explicitly described as an "in vitro diagnostic test" intended for "simultaneous detection and identification of multiple potentially pathogenic fungal organisms in positive blood culture," and its results "aid in the diagnosis of bloodstream infection."
No
The device description clearly outlines a physical instrument (GenMark's ePlex Instrument) and a physical test panel (ePlex Blood Culture Identification Fungal Pathogen (BCID-FP) Panel) that involves nucleic acid extraction, PCR, and hybridization using physical components like magnetic beads, a printed circuit board (PCB), and electrodes. This is a hardware-based in vitro diagnostic device with associated software for control and analysis, not a software-only medical device.
Yes, this device is an IVD (In Vitro Diagnostic).
The "Intended Use / Indications for Use" section explicitly states: "The GenMark ePlex Blood Culture Identification Fungal Pathogen (BCID-FP) Panel is a qualitative nucleic acid multiplex in vitro diagnostic test intended for use on GenMark's ePlex Instrument for simultaneous detection and identification of multiple potentially pathogenic fungal organisms in positive blood culture."
This statement clearly identifies the device as an in vitro diagnostic test.
N/A
Intended Use / Indications for Use
The GenMark ePlex Blood Culture Identification Fungal Pathogen (BCID-FP) Panel is a qualitative nucleic acid multiplex in vitro diagnostic test intended for use on GenMark's ePlex Instrument for simultaneous detection and identification of multiple potentially pathogenic fungal organisms in positive blood culture. The ePlex BCID-FP Panel is performed directly on blood culture samples identified as positive by a continuous monitoring blood culture system and which contain fungal organism.
The following fungal organisms are identified using the ePlex BCID-FP Panel: Candida albicans, Candida auris, Candida dubliniensis, Candida famata, Candida glabrata, Candida guilliermondii, Candida kefyr, Candida krusei, Candida lusitaniae, Candida parapsilosis, Candida tropicalis, Cryptococcus gattii, Cryptococcus neoformans, Fusarium and Rhodotorula.
The detection and identification of specific fungal nucleic acids from individuals exhibiting signs and/or symptoms of bloodstream infection aids in the diagnosis of bloodstream infection when used in conjunction with other clinical information. The results from the ePlex BCID-FP 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-FP 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-FP Panel, susceptibility testing and differentiation of mixed growth) and clinical presentation must be taken into consideration in the final diagnosis of bloodstream infection.
Product codes
PEO
Device Description
The ePlex Blood Culture Identification Fungal Pathogen (BCID-FP) 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.
Mentions image processing
Not Found
Mentions AI, DNN, or ML
Not Found
Input Imaging Modality
Not Found
Anatomical Site
bloodstream
Indicated Patient Age Range
all ages and genders
Intended User / Care Setting
Not Found
Description of the training set, sample size, data source, and annotation protocol
Not Found
Description of the test set, sample size, data source, and annotation protocol
A total of 866 positive blood culture samples with a Gram stain result indicating fungal organism consisting of 11 fresh prospective, 10 frozen prospective, 120 retrospective, and 725 contrived samples were evaluated for the ePlex BCID-FP Panel targets.
Prospective: Samples collected at 6 clinical sites. 11 fresh and 10 frozen samples.
Retrospective: 120 samples collected retrospectively from a total of 9 sites.
Contrived: 725 samples. 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.
Comparator Method: The performance of the ePlex BCID-FP Panel was compared to standard laboratory procedures, including traditional and automated culture, MALDI-TOF IVD, and microbiological and biochemical techniques. In addition, all prospective samples were tested with analytically validated PCR assays followed by bi-directional sequencing to determine the presence or absence of Candida auris, Fusarium, and Rhodotorula. Identification for samples with Candida parapsilosis identified by standard laboratory procedures was confirmed using analytically validated PCR assays followed by bi-directional sequencing. The comparator method(s) results were used to determine the Detected / Not Detected status for each target organism on the ePlex BCID-FP Panel.
Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)
Clinical Performance Study:
Study Type: Prospective, multicenter clinical study; also included retrospective and contrived samples.
Sample Size: A total of 866 positive blood culture samples (11 fresh prospective, 10 frozen prospective, 120 retrospective, and 725 contrived).
Key Results:
Sensitivity (PPA) and Specificity (NPA) were calculated for each target organism across different sample types (Prospective (Fresh), Prospective (Frozen), Prospective (All), Retrospective, Prospective/Retrospective, Contrived, Overall).
For most target organisms, the overall sensitivity/PPA and specificity/NPA were very high, often 100% or close to it, with narrow 95% confidence intervals.
For example, for Candida albicans (Overall): PPA = 97.1% (89.9-99.2%) and NPA = 99.9% (99.3-100%).
For Candida auris (Overall): PPA = 100% (92.7-100%) and NPA = 100% (99.5-100%).
One false negative for Candida albicans (Retrospective, 49/50), one for Candida guilliermondii (Contrived, 49/50), and two for Rhodotorula (Overall, 50/52).
Some false positives were re-investigated using PCR/sequencing and were detected, indicating potential limitations of the comparator method for those specific cases (e.g., C. glabrata, C. parapsilosis, C. tropicalis).
Analytical Performance Characteristics:
Limit of Detection (LOD) / Analytical Sensitivity:
Each assay's LOD was identified and verified using at least two quantified reference strains in simulated blood culture sample matrix. LOD was defined as the lowest concentration detected in ≥95% of tested replicates. LOD values ranged from 1 x 10^3 CFU/mL to 1 x 10^6 CFU/mL for various organisms.
Analytical Reactivity (Inclusivity):
51 strains/isolates were evaluated. All organisms tested at bottle positive concentrations were detected.
Predicted (in silico) Reactivity:
In silico analysis for Fusarium and Rhodotorula genus-level assays confirmed high predicted reactivity for most species within these genera.
Analytical Specificity (Cross-Reactivity and Exclusivity):
No cross-reactivity was observed for any of the 23 on-panel and 77 off-panel organisms tested.
Bottle Positivity:
Estimated bottle positivity concentrations for various organisms were equivalent to or greater than their established LODs.
Reproducibility:
Tested across three sites, with two operators, over six days, using three cartridge lots. High percent agreement with expected results demonstrated good reproducibility for all tested concentrations and organisms, usually at or near 100%.
Interfering Substances and Sample Matrix Equivalency (Bottle Evaluation):
No interference was observed from 18 common endogenous or exogenous substances at clinically relevant concentrations.
Thirteen out of fifteen bottle types tested showed no interference. One lot of BACT/Alert® PF Plus showed lower sensitivity for Rhodotorula, and one lot of BACT/Alert® FA Plus showed lower sensitivity for Candida albicans.
Carryover and Cross-Contamination:
No false positives were detected, indicating no carryover or cross-contamination.
Competitive Inhibition Study:
No competitive inhibition was observed in any of the simulated dual infection sample mixes tested.
Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)
Sensitivity (PPA): Range from 94.7% to 100% (Overall for individual targets).
Specificity (NPA): Range from 99.8% to 100% (Overall for individual targets).
Specific Examples (Overall Performance):
Candida albicans: Sensitivity/PPA: 97.1% (89.9-99.2%), Specificity/NPA: 99.9% (99.3-100%)
Candida auris: Sensitivity/PPA: 100% (92.7-100%), Specificity/NPA: 100% (99.5-100%)
Candida dubliniensis: Sensitivity/PPA: 100% (93.1-100%), Specificity/NPA: 100% (99.5-100%)
Candida famata: Sensitivity/PPA: 100% (93.0-100%), Specificity/NPA: 100% (99.5-100%)
Candida glabrata: Sensitivity/PPA: 98.3% (91.1-99.7%), Specificity/NPA: 99.8% (99.1-99.9%)
Candida guilliermondii: Sensitivity/PPA: 98.0% (89.5-99.6%), Specificity/NPA: 100% (99.5-100%)
Candida kefyr: Sensitivity/PPA: 100% (93.0-100%), Specificity/NPA: 99.8% (99.1-99.9%)
Candida krusei: Sensitivity/PPA: 100% (92.9-100%), Specificity/NPA: 100% (99.5-100%)
Candida lusitaniae: Sensitivity/PPA: 98.0% (89.3-99.6%), Specificity/NPA: 99.9% (99.3-100%)
Candida parapsilosis: Sensitivity/PPA: 98.3% (91.1-99.7%), Specificity/NPA: 99.9% (99.3-100%)
Candida tropicalis: Sensitivity/PPA: 100% (92.9-100%), Specificity/NPA: 99.9% (99.3-100%)
Cryptococcus gattii: Sensitivity/PPA: 100% (92.9-100%), Specificity/NPA: 100% (99.5-100%)
Cryptococcus neoformans: Sensitivity/PPA: 100% (93.7-100%), Specificity/NPA: 100% (99.5-100%)
Fusarium: Sensitivity/PPA: 98.6% (92.3-99.7%), Specificity/NPA: 100% (99.5-100%)
Rhodotorula: Sensitivity/PPA: 96.2% (87.0-98.9%), Specificity/NPA: 99.9% (99.3-100%)
Predicate Device(s)
Reference Device(s)
Not Found
Predetermined Change Control Plan (PCCP) - All Relevant Information
Not Found
§ 866.3365 Multiplex nucleic acid assay for identification of microorganisms and resistance markers from positive blood cultures.
(a)
Identification. A multiplex nucleic acid assay for identification of microorganisms and resistance markers from positive blood cultures is a qualitative in vitro device intended to simultaneously detect and identify microorganism nucleic acids from blood cultures that test positive by Gram stain or other microbiological stains. The device detects specific nucleic acid sequences for microorganism identification as well as for antimicrobial resistance. This device aids in the diagnosis of bloodstream infections when used in conjunction with other clinical and laboratory findings. However, the device does not replace traditional methods for culture and susceptibility testing.(b)
Classification. Class II (special controls). The special control for this device is FDA's guideline document entitled “Class II Special Controls Guideline: Multiplex Nucleic Acid Assay for Identification of Microorganisms and Resistance Markers from Positive Blood Cultures.” For availability of the guideline document, see § 866.1(e).
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Image /page/0/Picture/0 description: The image contains the logo of the U.S. Food and Drug Administration (FDA). On the left is the Department of Health and 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 21, 2018
GenMark Diagnostics, Incorporated Beth Stofka Sr. Regulatory Affairs Specialist 5964 La Place Court Carlsbad, California 92008
Re: K182690
Trade/Device Name: ePlex Blood Culture Identification Fungal Pathogen (BCID-FP) 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: PEO Dated: September 26, 2018 Received: September 27, 2018
Dear Beth Stofka:
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 mav, 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 avare 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 statutes and regulations administered by other Federal agencies. You must comply with all the Act's
1
requirements, including, but not limited to: registration and listing (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 (OS) 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
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Indications for Use
510(k) Number (if known) K182690
Device Name
ePlex Blood Culture Identification Fungal Pathogen (BCID-FP) Panel
Indications for Use (Describe)
The GenMark ePlex Blood Culture Identification Fungal Pathogen (BCID-FP) Panel is a qualitative nucleic acid multiplex in vitro diagnostic test intended for use on GenMark's ePlex Instrument for simultaneous detection and identification of multiple potentially pathogenic fungal organisms in positive blood culture. The ePlex BCID-FP Panel is performed directly on blood culture samples identified as positive by a continuous monitoring blood culture system and which contain fungal organism.
The following fungal organisms are identified using the ePlex BCID-FP Panel: Candida albicans, Candida auris, Candida dubliniensis, Candida famata, Candida glabrata, Candida guilliermondii, Candida kefyr, Candida krusei, Candida lusitaniae, Candida parapsilosis, Candida tropicalis, Cryptococcus gattii, Cryptococcus neoformans, Fusarium and Rhodotorula.
The detection and identification of specific fungal nucleic acids from individuals exhibiting signs and/or symptoms of bloodstream infection aids in the diagnosis of bloodstream infection when used in conjunction with other clinical information. The results from the ePlex BCID-FP 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-FP 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-FP Panel, susceptibility testing and differentiation of mixed growth) and clinical presentation must be taken into consideration in the final diagnosis of bloodstream infection.
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X Prescription Use (Part 21 CFR 801 Subpart D)
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510(k) Summary
Summary of Safety and Effectiveness
Submitter Information
| Submitter: | GenMark Diagnostics, Incorporated
5964 La Place Court
Carlsbad, CA 92008 |
|------------------------------------|---------------------------------------------------------------------------------------|
| Manufacturer: | GenMark Diagnostics, Incorporated
5964 La Place Court
Carlsbad, CA 92008 |
| Establishment Registration Number: | 3008632402 |
| Contact: | Beth Stofka
Sr. Regulatory Affairs Specialist |
| Phone: | 760-579-4778 |
| Fax: | 760-683-6961 |
| E-mail: | Beth.Stofka@genmarkdx.com |
| Alternate 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 |
| Date Prepared: | September 27, 2018 |
Name of Device and Classification
ePlex® Blood Culture Identification Fungal Pathogen (BCID-FP) Panel Product Name: Device Classification: 866.3980, Multiplex nucleic acid assay for identification of microorganisms and resistance markers from positive blood cultures, Class II Product Code(s): PEO
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Predicate Device
Predicate:
FilmArray Blood Culture Identification Panel; BioFire Diagnostics; K130914
Device Description
The ePlex Blood Culture Identification Fungal Pathogen (BCID-FP) 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 Fungal Pathogen (BCID-FP) Panel is a qualitative nucleic acid multiplex in vitro diagnostic test intended for use on GenMark's ePlex Instrument for simultaneous detection and identification of multiple potentially pathogenic fungal organisms in positive blood culture. The ePlex BCID-FP Panel is performed directly on blood culture samples identified as positive by a continuous monitoring blood culture system and which contain fungal organism.
The following fungal organisms are identified using the ePlex BCID-FP Panel: Candida albicans, Candida auris, Candida dubliniensis, Candida famata, Candida glabrata, Candida guilliermondii, Candida kefyr, Candida krusei, Candida lusitaniae, Candida parapsilosis, Candida tropicalis, Cryptococcus gattii, Cryptococcus neoformans, Fusarium and Rhodotorula.
The detection and identification of specific fungal nucleic acids from individuals exhibiting signs and/or symptoms of bloodstream infection aids in the diagnosis of bloodstream infection when used in conjunction with other clinical information. The results from the ePlex BCID-FP 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-FP 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-FP Panel, susceptibility testing and differentiation of mixed growth) and clinical presentation must be taken into consideration in the final diagnosis of bloodstream infection.
7
Summary of Technological Characteristics of the Device Compared to the Predicate Device
The GenMark ePlex Blood Culture Identification Fungal Pathogen (BCID-FP) Panel ("Subject Device") and the legally marketed device, FilmArray Blood Culture Identification Panel, K130914, ("Predicate Device") are described below:
| Characteristic | Subject Device | Predicate Device |
|---|---|---|
| Product Name | ePlex BCID-FP Panel | FilmArray BCID Panel |
| Manufacturer | GenMark Diagnostics, Inc. | BioFire Diagnostics, Inc. |
| Organisms | ||
| Detected | • Candida albicans | |
| • Candida auris | ||
| • Candida dubliniensis, | ||
| • Candida famata | ||
| • Candida glabrata | ||
| • Candida guilliermondii | ||
| • Candida kefyr | ||
| • Candida krusei | ||
| • Candida lusitaniae | ||
| • Candida parapsilosis | ||
| • Candida tropicalis | ||
| • Cryptococcus gattii | ||
| • Cryptococcus neoformans | ||
| • Fusarium | ||
| • Rhodotorula | 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, | ||
| Klebsiella pneumoniae, Proteus, and | ||
| Serratia marcescens), Haemophilus | ||
| influenzae, Neisseria meningitidis | ||
| (encapsulated), Pseudomonas | ||
| aeruginosa, Candida albicans, | ||
| Candida glabrata, Candida krusei, | ||
| Candida parapsilosis, and Candida | ||
| tropicalis. | ||
| Indication for | ||
| Use | The ePlex BCID-FP Panel is indicated | |
| as an aid in the diagnosis of | ||
| bloodstream infections. The use of | ||
| additional laboratory testing (e.g. sub- | ||
| culturing of positive blood cultures for | ||
| identification of organisms not detected | ||
| by the ePlex BCID-FP Panel and for | ||
| susceptibility testing, differentiation of | ||
| mixed growth) 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. | ||
| Characteristic | Subject Device | Predicate Device |
| Specimen Type | Blood culture samples identified as | |
| positive by a continuous monitoring | ||
| blood culture system and which | ||
| contain fungal organism. | Blood culture samples identified as | |
| positive by a continuous monitoring | ||
| blood culture system that demonstrates | ||
| the presence of organisms as | ||
| confirmed by Gram stain. | ||
| 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-FP 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. |
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9
Summary of Performance Data
EXPECTED VALUES
A prospective, multicenter clinical study was conducted to evaluate the clinical performance of the ePlex BCID-FP Panel in positive blood culture samples. A total of 447 positive blood culture samples were collected at 6 clinical sites in 2 phases from patients of all ages and genders. Samples were collected and frozen for future testing from May 2015 through July 2016. Samples were collected from July through August 2018 and tested fresh (never frozen). Of these 447 samples, 21 had a Gram stain result indicating fungal organism. The expected values of individual analytes based on the ePlex BCID-FP Panel results in the 21 prospective samples are summarized by age group and by site in Tables 1 and 2 below.
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| Target | All Ages
(N=21)
n (%) | Age Candida metapsilosis* | Trichosporon asahii* | 1 (0) | |
A. A discrepant organism is defined as one that was detected by the comparator method(s) but not by the BCID-FP Panel (excludes organisms not targeted by the BCID-FP Panel).
- Off-panel organism not targeted by the BCID-FP Panel.
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| Distinct Organism Combinations Detected by the
Comparator Method in Retrospective Samples | | | Number of Samples
(Number
Discrepant) | Discrepant
Organism(s)A |
|----------------------------------------------------------------------------------------------|-------------------------|------------------|---------------------------------------------|----------------------------|
| Target 1 | Target 2 | Target 3 | | |
| Candida
albicans | Candida
dubliniensis | Candida glabrata | 1 (1) | C. glabrata (1) |
| Candida
albicans | Candida
parapsilosis | | 1 (1) | C. parapsilosis (1) |
Table 25: Co-Detections Identified by the Comparator Method (Retrospective Samples)
A discrepant organism is defined as one that was detected by the comparator method(s) but not by the BCID-FP Panel A. (excludes organisms not targeted by the BCID-FP Panel).
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Clinical Study ePlex Instrument Performance
A total of 867 samples (including prospective, retrospective, and contrived samples) were initially tested in the clinical evaluations. Of these, 7/867 (0.8%) did not complete the run and the sample was retested. After repeat testing, all 867 sampleted testing and 839/867 (96.8%, 95% CI: 95.4%-97.8%) generated valid results and 28/867 (3.2%, 95% CI: 2.2%-4.6%) generated invalid results on the first completed attempt.
Upon repeat testing of the 28 samples with initially invalid results, all completed the run and 27/28 (96.4%) generated valid results. Overall, after final testing, 1/867 (0.1%, 95% CI: 0.0%-0.7%) had final, invalid results, resulting in a final validity rate of 866/867 (99.9%, 95% CI: 99.3%-100%).
Analytical Performance Characteristics
Limit of Detection (Analytical Sensitivity)
The Limit of Detection (LOD), or analytical sensitivity, was identified and verified for each assay on the BCID-FP Panel using at least two quantified reference strains in simulated blood culture sample matrix, which is defined as whole blood with EDTA added to a blood culture bottle in the same ratio as the manufacturer recommends and incubated for 8 hours. At least 20 replicates per target were tested for each condition. The limit of detection was defined as the lowest concentration of each target that is detected in ≥95% of tested replicates. The confirmed LOD for each ePlex BCID-FP Panel organism is shown in Table 26.
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Table 26: LOD Results Summary
| Target | Organism | Strain | LOD
Concentration
(CFU/mL) |
|-------------------------|--------------------------|-------------------|----------------------------------|
| Candida albicans | Candida albicans | ATCC 14053 | $1 x 10^6$ |
| | Candida albicans | ATCC 24433 | $1 x 10^5$ |
| Candida auris | Candida auris | CBS 10913 | $1 x 10^5$ |
| | Candida auris | CBS 12766 | $1 x 10^5$ |
| Candida dubliniensis | Candida dubliniensis | ATCC MYA-
577 | $1 x 10^4$ |
| | Candida dubliniensis | NCPF 3949 | $1 x 10^5$ |
| Candida famata | Candida famata | CBS 767 | $1 x 10^3$ |
| | Candida famata | CBS 766 | $1 x 10^4$ |
| Candida glabrata | Candida glabrata | ATCC 2001 | $1 x 10^6$ |
| | Candida glabrata | ATCC 15545 | $1 x 10^6$ |
| Candida guilliermondii | Candida guilliermondii | ATCC 22017 | $1 x 10^5$ |
| | Candida guilliermondii | ATCC 6260 | $1 x 10^5$ |
| Candida kefyr | Candida kefyr | ATCC 4135 | $1 x 10^3$ |
| | Candida kefyr | ATCC 8553 | $1 x 10^4$ |
| Candida krusei | Candida krusei | ATCC 22985 | $1 x 10^5$ |
| | Candida krusei | ATCC 28870 | $1 x 10^6$ |
| Candida lusitaniae | Candida lusitaniae | ATCC 34449 | $1 x 10^6$ |
| | Candida lusitaniae | ATCC 66035 | $1 x 10^5$ |
| Candida parapsilosis | Candida parapsilosis | ATCC 28474 | $1 x 10^4$ |
| | Candida parapsilosis | ATCC 28475 | $1 x 10^5$ |
| Candida tropicalis | Candida tropicalis | ATCC 13803 | $1 x 10^5$ |
| | Candida tropicalis | ATCC 1369 | $1 x 10^6$ |
| Cryptococcus gattii | Cryptococcus gattii | ATCC MYA-
4877 | $1 x 10^3$ |
| Target | Organism | Strain | LOD
Concentration
(CFU/mL) |
| | Cryptococcus gattii | ATCC MYA-
4138 | 1 x 103 |
| Cryptococcus neoformans | Cryptococcus neoformans | ATCC 208821 | 1 x 105 |
| | Cryptococcus neoformans | ATCC MYA-
565 | 1 x 105 |
| Fusarium | Fusarium oxysporum | CBS 116611 | 1 x 106
spores/mL |
| | Fusarium solani | ATCC 36301 | 1 x 106
spores/mL |
| Rhodotorula | Rhodotorula mucilaginosa | ATCC 4058 | 1 x 105 |
| | Rhodotorula glutinis | ATCC 32765 | 1 x 105 |
| Target | Organism | Strain | |
| Candida albicans | Candida albicans | ATCC 10231 | |
| | Candida albicans | ATCC 90028 | |
| | Candida albicans | ATCC MYA-4441 | |
| Candida auris | Candida auris | CDC#385 | |
| | Candida auris | CDC#386 | |
| | Candida auris | CDC#387 | |
| | Candida auris | CDC#388 | |
| | Candida auris | CDC#389 | |
| | Candida auris | CDC#390 | |
| | Candida auris | CBS 12766 | |
| Candida dubliniensis | Candida dubliniensis | ATCC MYA-578 | |
| | Candida dubliniensis | ATCC MYA-579 | |
| | Candida dubliniensis | ATCC MYA-582 | |
| Candida famata | Candida famata | ATCC 20850 | |
| | Candida famata | CBA 1961 | |
| | Candida famata | CBS 789 | |
| Candida glabrata | Candida glabrata | ATCC 15126 | |
| | Candida glabrata | ATCC 66032 | |
| | Candida glabrata | ATCC MYA-2950 | |
| Candida guilliermondii | Candida guilliermondii | ATCC 90197 | |
| | Candida guilliermondii | ATCC 90198 | |
| | Candida guilliermondii | ATCC 90199 | |
| Candida kefyr | Candida kefyr | ATCC 204093 | |
| | Candida kefyr | ATCC 2512 | |
| | Candida kefyr | ATCC 66028 | |
| Candida krusei | Candida krusei | ATCC 14243 | |
| | Candida krusei | ATCC 32196 | |
| | Candida krusei | ATCC 34135 | |
| Candida lusitaniae | Candida lusitaniae | ATCC 42720 | |
| | Candida lusitaniae | ATCC MYA-766 | |
| | Candida lusitaniae | Z010 | |
| Candida parapsilosis | Candida parapsilosis | ATCC 22019 | |
| | Candida parapsilosis | ATCC 58895 | |
| | Candida parapsilosis | ATCC 90018 | |
| Candida tropicalis | Candida tropicalis | ATCC 201380 | |
| | Candida tropicalis | ATCC 201381 | |
| Target | Organism | Strain | |
| | Candida tropicalis | ATCC 750 | |
| Cryptococcus gattii | Cryptococcus gattii | ATCC 14248 | |
| Cryptococcus gattii | Cryptococcus gattii | ATCC 4560 | |
| Cryptococcus gattii | Cryptococcus gattii | ATCC 76108 | |
| Cryptococcus neoformans | Cryptococcus neoformans | ATCC 14116 | |
| Cryptococcus neoformans | Cryptococcus neoformans | ATCC 90112 | |
| Cryptococcus neoformans | Cryptococcus neoformans | NCPF 8299 | |
| Fusarium | Bisifusarium dimerum | CBS 110317 | |
| Fusarium | Fusarium moniliforme | ATCC 38159 | |
| Fusarium | Fusarium proliferatum | CBS 131570 | |
| Fusarium | Fusarium sacchari | CBS 119828 | |
| Fusarium | Fusarium verticillioides | CBS 100312 | |
| Rhodotorula | Rhodotorula glutinis | ATCC 96365 | |
| Rhodotorula | Rhodotorula mucilaginosa | ATCC 66034 | |
| Rhodotorula | Rhodotorula mucilaginosa | ATCC 9449 | |
32
Analytical Reactivity (Inclusivity)
A panel of 51 strains/isolates, representing the genetic, temporal and geographic diversity of each target on the ePlex BCID-FP Panel was evaluated to demonstrate analytical reactivity. Each strain was tested in triplicate at concentrations approximating bottle positivity (1 x 10° CFU/mL for Candida and Rhodotorula, 1 x 107 CFU/mL for Cryptococcus, and 1 x 108 spores/mL for Fusarium). All organisms tested were detected at bottle positive concentrations. Results of the analytical reactivity are summarized in Table 27. An additional 29 unique strains were detected as a part of the Limit of Detection (Analytical Sensitivity) study and are summarized in Table 26.
33
Table 27: Analytical Reactivity (Inclusivity) Results
34
35
Predicted (in silico) Reactivity for Genus and Group Assays
Note: the performance of the ePlex BCID-FP Panel has not been established for all of the organisms listed in the tables below. See the Analytical Reactivity (Inclusivity) and Limit of Detection (Analytical Sensitivity) sections of the package insert for data on organisms for which performance characteristics have been established (indicated with an asterisk in Tables 32 and 33). Some species were not assessed in silico due to lack of sequence data, though they may appear in the analytical sensitivity or specificity studies.
In addition to species-specific assays, the ePlex BCID-FP Panel contains two broader genuslevel assays: Fusarium and Rhodotorula. Table 28 and Table 29 highlight the predicted (in silico) reactivity (inclusivity) for these assay targets.
| Detection Predicted for ≥95% of target sequences | ||
|---|---|---|
| Fusarium acaciae-mearnsii | Fusarium cortaderiae | Fusarium napiforme |
| Fusarium acuminatum | Fusarium culmorum | Fusarium nisikadoi |
| Fusarium acutatum | Fusarium denticulatum | Fusarium nygamai |
| Fusarium aethiopicum | Bisifusarium dimerum* | Fusarium oxysporum* |
| Fusarium ananatum | Fusarium dlaminii | Fusarium palustre |
| Fusarium andiyazi | Fusarium equiseti | Fusarium phyllophilum |
| Fusarium anthophilum | Fusarium falciforme | Fusarium poae |
| Fusarium armeniacum | Fusarium foetens | Fusarium polyphialidicum |
| Fusarium asiaticum | Fusarium fujikuroi | Fusarium proliferatum* |
| Fusarium austroamericanum | Fusarium gaditjirri | Fusarium pseudoanthophilum |
| Fusarium avenaceum | Fusarium globosum | Fusarium pseudocircinatum |
| Fusarium aywerte | Fusarium guttiforme | Fusarium pseudograminearum |
| Fusarium bactridioides | Fusarium hostae | Fusarium pseudonygamai |
| Fusarium begoniae | Fusarium incarnatum | Fusarium ramigenum |
| Fusarium beomiforme | Fusarium inflexum | Fusarium sacchari* |
| Fusarium boothii | Fusarium konzum | Fusarium secorum |
| Fusarium brachygibbosum | Fusarium lacertarum | Fusarium sinensis |
| Fusarium brasilicum | Fusarium lactis | Fusarium solani* |
| Fusarium brevicatenulatum | Fusarium langsethiae | Fusarium sporotrichioides |
| Fusarium bulbicola | Fusarium lichenicola | Fusarium sterilihyphosum |
Table 28: Predicted (in silico) Reactivity (Inclusivity) Results for Fusarium
36
| (Cylindrocarpon lichenicola) | ||
|---|---|---|
| Fusarium bullatum | Fusarium louisianense | Fusarium subglutinans |
| Fusarium camptoceras | Fusarium lunulosporum | Fusarium temperatum |
| Fusarium cerealis | Fusarium mangiferae | Fusarium thapsinum |
| Fusarium circinatum | Fusarium meridionale | Fusarium udum |
| Fusarium commune | Fusarium mesoamericanum | Fusarium verticillioides* |
| Fusarium concentricum | Fusarium mexicanum | |
| Fusarium concolor | Fusarium musae | |
| Detection Predicted for 85%-94% of target sequences | ||
| Fusarium torulosum | Fusarium xylarioides | |
| Detection Predicted for |