The ePlex Instrument is an automated in vitro diagnostic (IVD) device designed to perform multiplexed nucleic acid tests for the simultaneous detection and identification of nucleic acid targets by processing single-use cartridges developed and manufactured by GenMark Diagnostics, Inc.

Device Description

The ePlex® Instrument is used to run single-use assay cartridges that incorporate digital microfluidics and GenMark's eSensor® detection technology (used by products that are currently FDA-cleared: K073720 and K090901) to automate all aspects of nucleic acid testing. The ePlex Instrument is designed to: provide a nucleic acid amplification testing solution directly from various sample types, provide random access testing capability, and require minimal operator interaction.

The ePlex Instrument includes the following components:

. Base: A touchscreen graphical user interface (GUI) powered by a PC with a Windows Operating System 7. The base communicates with the bays to transfer data. The instrument software installed on the ePlex base processes the raw data generated by the individual bays and determines the test result.
Tower: A chassis housing six bays. ePlex is scalable from one to four towers . connected to either side of the base.
. Bay: 6 bays are housed in each tower. Each bay will accept cartridges independent of the testing status of the other bays allowing for random access testing. Each bay has an Ethernet port for communication with the base unit to receive user inputs and deliver test data to the ePlex Instrument software.

The touchscreen graphical user interface (GUI) is flanked on either side by a tower with six bays containing a slot for the cartridge and an LED to indicate bay status (in-use or available for use). The instrument is designed to be scalable with configurations to accommodate a single tower with 6 bays or up to four towers with 24 bays.

The ePlex system is used to run multiplex microarray-based assays developed by GenMark. This type of assay is based on the principles of competitive nucleic acid hybridization using a sandwich assay format, wherein a single-stranded target binds concurrently to a sequencespecific 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, singlestranded 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.

AI/ML Overview

Here's an analysis of the acceptance criteria and study information provided for the GenMark Diagnostics, Inc. ePlex Instrument, based on the provided text:

Important Note: The provided document is a 510(k) summary for the ePlex Instrument itself, not a specific assay. It states that detailed clinical performance data will be included in the traditional 510(k) for the ePlex RP Panel. Therefore, the information below primarily relates to the instrument's performance as demonstrated through a reproducibility study, rather than the diagnostic accuracy of a specific assay.

1. Table of Acceptance Criteria and Reported Device Performance

The document mentions that acceptance criteria were established in advance for the reproducibility study and all were met. However, it does not explicitly list the quantitative acceptance criteria or the specific reported device performance metrics (e.g., specific percentages for run validity, agreement, or variability) for the ePlex Instrument in the provided text.

In the context of the ePlex Instrument, the reported performance is qualitative:

Type of Performance Metric	Acceptance Criteria	Reported Device Performance
Run Validity	Established in advance (not explicitly stated in document)	Met
Agreement	Established in advance (not explicitly stated in document)	Met
Variability	Established in advance (not explicitly stated in document)	Met

2. Sample Size and Data Provenance for the Test Set

Test Set Description: The test set for the reproducibility study consisted of samples prepared at three concentration levels: moderate (3x LoD), low (1x LoD), and negative. These samples were run as a panel.
Sample Size: The exact number of individual samples or runs used in the reproducibility study is not specified in the provided document. It states "samples prepared as a panel at moderate (3x LoD), low (1x LoD) and negative."
Data Provenance: The study was conducted at three separate testing sites, implying multi-site data collection. The country of origin is not explicitly stated, but given the FDA submission, it is likely the United States. It was a prospective study as it was specifically conducted to evaluate the instrument's reproducibility.

3. Number of Experts and Qualifications for Ground Truth

Ground Truth Establishment: For the reproducibility study of the instrument, the ground truth would likely be based on the known state of the prepared samples (i.e., 'positive' at specific concentrations or 'negative'). Therefore, the concept of "experts establishing ground truth" in the traditional sense (e.g., radiologists reviewing images) is not directly applicable here. The ground truth is intrinsic to the sample preparation.
Number of Experts: Not applicable in this context.
Qualifications of Experts: Not applicable in this context.

4. Adjudication Method for the Test Set

Adjudication Method: Not applicable. The nature of a reproducibility study with pre-defined positive/negative samples at specific concentrations doesn't typically involve expert adjudication of results. The "truth" is determined by the sample preparation.

5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study

MRMC Study: No, a multi-reader multi-case (MRMC) comparative effectiveness study was not mentioned as part of the ePlex Instrument's submission. This type of study would be more relevant for evaluating the impact of an AI-powered diagnostic algorithm on human performance, which is not the primary focus of this instrument submission.
Effect Size: Not applicable.

6. Standalone Performance Study

Standalone Performance: Yes, the reproducibility study evaluated the standalone performance of the ePlex Instrument. It assessed the instrument's ability to consistently generate results based on its internal processes (cell disruption, nucleic acid extraction, RT-PCR, single-stranding, signal detection) when processing known samples. The study evaluated "run validity, agreement, and variability."

7. Type of Ground Truth Used

Ground Truth Type: The ground truth used was based on known sample preparation. Samples were intentionally prepared at specific concentrations (3x Limit of Detection, 1x Limit of Detection) or as negative controls. This is a form of analytical gold standard derived from controlled experimental design.

8. Sample Size for the Training Set

Training Set Size: The document does not specify a separate training set size for the ePlex Instrument itself. This is expected because the ePlex Instrument is hardware, and while it contains software, the "training" in the AI/machine learning sense isn't explicitly discussed here for the instrument's core functions. Any algorithm "training" would likely be specific to individual assays run on the instrument (e.g., for interpreting an RP panel), and that information is deferred to the specific assay 510(k) submission.

9. How Ground Truth for the Training Set Was Established

Ground Truth Establishment for Training Set: Since a separate training set for the instrument's core functionality is not described, the method of establishing ground truth for such a set is not provided in this document. If the instrument's software incorporates machine learning for result interpretation (beyond simple thresholding), that information would typically be detailed in the specific assay submission for which the training was performed.

Summary

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Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002

June 9, 2017

GENMARK DIAGNOSTICS, INCORPORATED ALAN MADERAZO, Ph.D., RAC VP OF QUALITY, REGULATORY & CLINICAL AFFAIRS 5964 La PLACE COURT CARLSBAD CA 92008

Re: K163652

Trade/Device Name: ePlex Instrument Regulation Number: 21 CFR 862.2570 Regulation Name: Instrumentation for clinical multiplex test systems Regulatory Class: II Product Code: NSU Dated: May 8, 2017 Received: May 9, 2017

Dear Dr. 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. 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 requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Parts 801 and 809); medical device reporting (reporting of medical device-related adverse events) (21 CFR 803); good manufacturing practice requirements as set forth in the quality systems (OS) regulation (21 CFR Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

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If you desire specific advice for your device on our labeling regulations (21 CFR Parts 801 and 809), please contact the Division of Industry and Consumer Education at its toll-free number (800) 638 2041 or (301) 796-7100 or at its Internet address

http://www.fda.gov/MedicalDevices/Resourcesfor You/Industry/default.htm. 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 the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance.

You may obtain other general information on your responsibilities under the Act from the Division of Industry and Consumer Education at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address

http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm.

Sincerely yours.

Stephen J. Lovell -S for

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) K163652

Device Name ePlex® Instrument

Indications for Use (Describe)

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)

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510(k) Summary

Summary of Information to Support Substantial Equivalence to Predicate Device

Submitter Information

Submitter:	GenMark Diagnostics, Incorporated5964 La Place CourtCarlsbad, CA 92008
Manufacturer:	GenMark Diagnostics, Incorporated5964 La Place CourtCarlsbad, CA 92008
Establishment Registration Number:	3008632402
Contact:	Alan Maderazo, Ph.D., RACVice President, Quality, Regulatory and Clinical Affairs
Phone:	760-448-4308
Fax:	760-683-6961
E-mail:	Al.Maderazo@genmarkdx.com
Alternate Contact:	Joseph McMullenConsultant, Regulatory Affairs
Phone:	760-410-5052
Fax:	760-683-6961
E-mail:	Joseph.McMullen@genmarkdx.com
Date Prepared:	December 21, 2016

Name of Device and Classification

Product Name:	ePlex® Instrument
Device Classification:	862.2570, Instrumentation for clinical multiplex test systems, Class II
Product Code:	NSU, Instrumentation for Clinical Multiplex Test Systems.

Predicate Device

Predicate:	BioFire Diagnostics FilmArray 2.0
------------	-----------------------------------

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Device Description

The ePlex Instrument includes the following components:

. Base: A touchscreen graphical user interface (GUI) powered by a PC with a Windows Operating System 7. The base communicates with the bays to transfer data. The instrument software installed on the ePlex base processes the raw data generated by the individual bays and determines the test result.
Tower: A chassis housing six bays. ePlex is scalable from one to four towers . connected to either side of the base.
. Bay: 6 bays are housed in each tower. Each bay will accept cartridges independent of the testing status of the other bays allowing for random access testing. Each bay has an Ethernet port for communication with the base unit to receive user inputs and deliver test data to the ePlex Instrument software.

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Intended Use/Indications for Use

Summary of Technological Characteristics of the Device Compared to the Predicate Device

The GenMark ePlex Instrument ("Subject Device") and the legally marketed device, BioFire FilmArray 2.0 ("Predicate Device") are described below:

Characteristic	Proposed Device	Predicate Device
Product Name	ePlex Instrument	FilmArray 2.0
Manufacturer	GenMark Diagnostics	BioFire Diagnostics
Regulation	862.2570Instrumentation for clinical multiplextest systems	862.2570Instrumentation for clinical multiplextest systems
Product Code	NSU: Instrumentation for ClinicalMultiplex Test Systems	NSU: Instrumentation for ClinicalMultiplex Test Systems
Device Class	Class II	Class II
Characteristic	Proposed Device	Predicate Device
Intended Use	The ePlex Instrument is an automatedin vitro diagnostic (IVD) devicedesigned to perform multiplexednucleic acid tests for the simultaneousdetection and identification of nucleicacid targets by processing single-usecartridges developed andmanufactured by GenMarkDiagnostics, Inc.	The FilmArray 2.0 is an automated inin vitro diagnostic (IVD) device designedfor use with FilmArray panels. TheFilmArray 2.0 is intended for use incombination with assay specificreagent pouches to detect multiplenucleic acid targets contained inclinical specimens. The FilmArray 2.0instrument interacts with the reagentpouch to both purify nucleic acids andamplify targeted nucleic acidsequences using nested multiplex PCRin a closed system. The resulting PCRproducts are evaluated using DNAmelting analysis. The softwareautomatically determines the resultsand provides a test report.The FilmArray 2.0 is composed of oneto eight instruments connected to acomputer running FilmArray 2.0software, which controls the functionof each instrument and collects,analyzes, and stores data generated byeach instrument.
Assays	For use with FDA cleared GenMarkdeveloped panels includingRespiratory Panel (RP).	For use with FDA cleared FilmArraypanels:Respiratory Panel (RP)Blood Culture Identification (BCID)Panel Gastrointestinal (GI) Panel
ProtocolProcessing Steps	Cell disruption, nucleic acidextraction, RT-PCR, single strandingand signal detection	Cell disruption, nucleic acid extraction,PCR1 thermocycling, PCR2thermocycling, DNA melt and signaldetection.
Time to result	Approximately 90 minutes (dependson ePlex assay cartridge)	Approximately 1 hour per sample
TechnologicalPrinciples	Multiplex nucleic acid amplification(including reverse transcription asappropriate) utilizing GenMarkproprietary electrowetting technology,followed by detection of analytetargets utilizing GenMark proprietaryeSensor® technology.	Nested multiplex nucleic acidamplification (including reversetranscription as appropriate) followedby high-resolution melting analysis toconfirm the identity of the amplifiedproduct.
RequiredAccessory	GenMark ePlex Cartridge (aka"consumable" or "assay cartridge"),and barcode scanner	FilmArray Reagent Pouch
SamplePreparationMethod	Minimal sample processing andhands-on time.	Minimal sample processing and hands-on time.
TestInterpretation	Automated test interpretation andreport generation. User cannot access	Automated test interpretation andreport generation. User cannot accessraw data. Report can be printed.
Characteristicand ResultsReporting	Proposed Device	Predicate Device
	raw data. Report can be printed,exported or sent to an LIS.
User Interface	Touch-screen base unit withintegrated PC on a Windowsoperating system.	FilmArray unit(s) plugged into astandalone PC operated on a Windowsoperating system.
User Complexity	Moderate	Moderate
DetectionProcedure	Cyclic voltammetry on custom PCB	Complimentary metal-oxidesemiconductor (CMOS) cameraHard-coated filters.
DetectionChemistries	Complimentary nucleic acid bindingwith ferrocene labeled probes	Melt curve analysis. Fluorescentimaging of PCR reactions.
Instrument-SoftwareCommunication	Communication travels via Ethernetcable/port.	Communication travels via Ethernetcable/port.Communication for multipleinstruments mediated by a multi-portswitch.
DeviceConfiguration	A base unit containing an integratedPC; with onscreen key board andtouch screen operation, anddetachable barcode scanner andmagnetic arm rest. Designed tosupport external keyboard and mouse.System is configurable with 1 to 4towers; each tower contains 6 bays.Towers are attached to the left andright sides of the base, a maximum of2 towers may be attached to each side.Printer provided with System andoptional Universal Power Supply(UPS) offered.Each bay has single-sample testcapacity.Random-access multi-sample testcapacity per system.	Up to eight FilmArray 2.0 instrumentsto one computer with mouse, barcodescanner and pouch loading station.Single-sample test capacity perinstrument with random-access multi-sample test capacity per system.Printer Provided with System.Interlocking two-instrument racksavailable to stack instruments andreduce system footprint. (Optional)Instrument held at 0° angle when norack is used. Instrument held at 15°angle on the rack.

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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 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. Comparison of device performance characteristics will be included in each respective GenMark assay 510(k).

Summary of Performance Data

Performance of the ePlex Instrument was evaluated in a reproducibility study using the GenMark ePlex Respiratory Pathogen (RP) Panel. GenMark will submit a traditional 510(k) for the ePlex RP Panel that will be used with the ePlex Instrument. Complete non-clinical and clinical performance data will be included in the traditional 510(k) for the ePlex RP Panel.

The reproducibility study utilized samples prepared as a panel at moderate (3x LoD), low (1x LoD) and negative. The study was conducted at three separate testing sites with different ePlex instruments, by multiple operators performing runs over several days. Run validity, agreement, and variability were analyzed. Acceptance criteria were established in advance of conducting the study and all acceptance criteria were met.

Regulation Number and Section

§ 862.2570 Instrumentation for clinical multiplex test systems.

(a)
Identification. Instrumentation for clinical multiplex test systems is a device intended to measure and sort multiple signals generated by an assay from a clinical sample. This instrumentation is used with a specific assay to measure multiple similar analytes that establish a single indicator to aid in diagnosis. Such instrumentation may be compatible with more than one specific assay. The device includes a signal reader unit, and may also integrate reagent handling, hybridization, washing, dedicated instrument control, and other hardware components, as well as raw data storage mechanisms, data acquisition software, and software to process detected signals.(b)
Classification. Class II (special controls). The device is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 862.9. The special control is FDA's guidance document entitled “Class II Special Controls Guidance Document: Instrumentation for Clinical Multiplex Test Systems.” See § 862.1(d) for the availability of this guidance document.