(168 days)
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.
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.
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.
§ 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.