(341 days)
The INFINITI™ System Assay for Factor II & Factor V is an in vitro diagnostic device that consists of reagents and instrumentation which includes polymerase chain reaction (PCR) primers, hybridization matrices, a thermal cycler, an imager, and software for detection and genotyping of Factor II (Prothrombin) G20210A and Factor V Leiden G1691A point mutations in DNA obtained from human blood samples. The INFINITI™ System Assay for Factor II & Factor V is a qualitative assay for use in clinical laboratories upon prescription by the attending physician.
The INFINITI" System Assay for detection and genotyping of Factor II & Factor V is indicated for use as an aid to diagnosis in the evaluation of patients with suspected thrombophilia.
The INFINITI System Assay for Factor II & Factor V is an in vitro diagnostic device which utilizes proprietary film-based microarray technology combined with process automation, reagent management and software technology for the detection and genotyping of the Factor II (Prothrombin) G20210A mutation and the Factor V Leiden G1691A mutation from deoxyribonucleic acid (DNA) isolated from human whole peripheral blood samples.
The INFINITI System Assay for Factor II & Factor V is comprised of the BioFilmChip" Microarray, the Intellipac™ Reagent Module, and the INFINITI Analyzer with the Qmatic" Operating Software.
The BioFilmChip Microarray consists of a polyester film coated with proprietary multi-layer components designed for DNA analysis. The layers have been designed to provide a versatile surface to enhance test performance. There can be up to 240 spots per microarray with each spot representing a different allele. The microarrays are designed to be assay specific.
The Intellipac Reagent Module which acts as a communication link contains up to eight reservoirs that house the test reagents and has an integrated memory chip. The assay protocol resides in this memory chip and upon request is loaded to the INFINITI Analyzer. Information such as expiration date of reagents, volume usage, time of use and operation parameters are archived in the memory chip and appear on the worklist (run report).
The INFINITI Analyzer is an instrument used for clinical multiplex systems intended to measure and sort multiple signals from a clinical sample. The INFINITI Analyzer is designed to measure fluorescence signals of labeled DNA target hybridized to BioFilmChip microarrays. The INFINITI Analyzer automates the Factor II and Factor V assays and integrates all the discrete processes of sample (PCR amplicon) handling, reagent management, hybridization, detection, and results analysis. The assays are processed automatically and read by the built-in confocal microscope. Results are analyzed and presented in numerical and graphical format.
The INFINITI Analyzer has two main components: pipetting and optics modules. A variety of electronic components inside the instrument are used for its operation. These include multiple stepper motors, heating and cooling devices, a barcode reader, a photomultiplier tube, and a camera all connected to USB ports.
Pipetting Module - The pipetting module performs all the operations related to dispensing and aspiration of reagent and processing the amplified sample to be dispensed on the microarray. When the sample has been processed and hybridized to the microarray, it is transferred to the optics module for scanning and reading.
Optics Module - The optics module is a lightproof assembly comprised of a 3-axis stage: camera, lasers, and a photo multiplier tube (PMT). It is the enclosed casement into which the microarray is transported automatically prior to being processed on the stringency station. The optics' stage follows X-Y-Z motions that can be stepped at a very precise rate (2.0 micron per step). Using excitation wavelengths of a 760nm laser diode, the camera takes a 1.2x1.2mm picture for each registration spot of a fluorescent die. Analyses of these pictures allow the location of three registration spots to be determined. With respect to the position of the three registration spots, coordinates of all the bio-spots can be located. While scanning, the stage moves along the Z-axis to focus the chip and the X and Y-axes to locate the individual spots on the microarray.
The INFINITI Analyzer hardware is controlled by the Qmatic™ operating software, which is installed with-in the on-board computer and utilizes a LCD screen display. The INFINITI Analyzer modules are controlled by multitasking real time software. The Omatic "M operating software has a schedule manager that is capable of controlling all operations of the INFINITI Analyzer such as assay protocol, fluid handling, robotics, optical detection and result analysis. Results are available for review via the LCD screen. Management reports include results in numerical and graphical format. The operator can also print the displayed results in tabular form (printer not included with INFINITI Analyzer).
Here's a breakdown of the acceptance criteria and the study information for the INFINITI™ System Assay for Factor II & Factor V, based on the provided 510(k) summary:
1. Table of Acceptance Criteria and Reported Device Performance
The 510(k) summary largely focuses on demonstrating equivalence to predicate devices and detailing performance characteristics rather than explicitly stating pre-defined "acceptance criteria" with specific thresholds for all metrics. However, we can infer the implied acceptance based on the reported results and the comparison to the predicate device.
| Feature | Acceptance Criteria (Inferred from Predicate Equivalence/Performance) | Reported Device Performance and Remarks |
|---|---|---|
| Percent Agreement with Predicate | - Factor II: >95% agreement with predicate device (Roche Factor II G20210A Kit) |
- Factor V: >95% agreement with predicate device (Roche Factor V Leiden Kit) | - Factor II: 98.6% agreement with predicate
- Factor V: 100.0% agreement with predicate |
| Limit of Detection (LoD) | Sufficient to detect mutations in typical clinical samples. | 1ng DNA/test. |
| Assay Precision/Reproducibility | - Chip-to-chip: Low CVs for wild-type calls, 100% correct genotype calls. - Lot-to-lot: No significant lot-to-lot difference (p>0.05) in RFU, 100% correct genotype calls.
- Day-to-day: Acceptable RFU signal %CV, 100% correct genotype calls. | - Chip-to-chip: CVs for wild-type present calls ranged from 9-12%. All calls were 100% correct.
- Lot-to-lot: Two-way ANOVA on RFU readings did not detect lot-to-lot difference on three of four test runs (p > 0.05). Detected lot-to-lot difference on one test run (0.05 > p > 0.01). Genotype calls were 100% correct.
- Day-to-day: RFU signal %CV ranged from 1.35-14.87 (Day 1), 0.77-19.72 (Day 2), and 0.41-21.2 (Day 3). Genotype calls were 100% correct. |
| Instrument Reproducibility | - Intra-Instrument: Acceptable %CV, 100% genotype call reproduction. - Inter-Instrument: Acceptable %CV, 100% correct and reproducible genotype calls. | - Intra-Instrument Reproducibility: %CV using a single chip five times on a single instrument ranged from 0.9 to 28.3%. Genotype calls were 100% reproduced within each instrument.
- Inter-Instrument Reproducibility: %CV using a single chip five times on each of three instruments ranged from 0.5% to 12%. All genotype calls were 100% correct and reproducible.
- Standard Microarray Chip: For three instruments, average %CV for capture probe spots ranged from 3.24% to 4.03%, with ranges per instrument from 1.9-7.5%. |
| Reagent Stability | Demonstrated stability for adequate shelf life. | - BioFilmChip Microarray: 90 days at RT (25-30 °C) - Intellipac Reagent Module: 90 days at 4°C
- Amplification Mix: 90 days at 4°C |
| Interference | No significant interference from common interferents. | No interference with 8mg/dL bilirubin, 70mg/dL cholesterol, and 1333μ/dL heparin. No studies conducted with oral anti-coagulants (no claims made). |
| Sample Carry-over | No detectable carry-over. | No carry-over detected when a series of positive and negative samples, followed by a "No Template Control," was run six times. |
2. Sample Sizes Used for the Test Set and Data Provenance
The "test set" here refers to the samples used for the comparative effectiveness study against the predicate device.
- Factor II G20210A mutation: 208 samples
- Factor V Leiden G1691A mutation: 175 samples
The document does not specify the country of origin of the data or whether it was retrospective or prospective.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Their Qualifications
This information is not provided in the given 510(k) summary. The ground truth for the comparison study was based on the results from the predicate devices (Roche Factor II G20210A and Factor V Leiden Kits). It's implied that the predicate devices themselves established the "ground truth" for the samples.
4. Adjudication Method for the Test Set
This information is not provided. The comparison was directly between the new device and the predicate device results. There's no mention of an independent adjudication process for discrepancies.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance
Not Applicable. This device is an in-vitro diagnostic (IVD) assay system and analyzer, not an AI-powered image analysis or diagnostic aid for human readers. Therefore, an MRMC study and analysis of human reader improvement with AI assistance is not relevant to this submission.
6. If a Standalone (i.e. algorithm only without human-in-the-loop performance) was done
Yes, the performance characteristics described, such as Limit of Detection, Assay Precision, Instrument Reproducibility, Reagent Stability, Interference, and Sample Carry-over, represent the standalone performance of the INFINITI™ System Assay for Factor II & Factor V. The comparison to the predicate device also assesses its standalone diagnostic performance.
7. The Type of Ground Truth Used
The ground truth for the comparative effectiveness study was established by the predicate devices: the Roche Factor II G20210A Kit and the Roche Factor V Leiden Kit. This means the device's accuracy was assessed by its agreement with these established, FDA-cleared methods.
8. The Sample Size for the Training Set
The document does not specify a separate "training set" size. As this is a molecular diagnostic assay system, the development process typically involves optimizing reagents and conditions rather than training a machine learning algorithm in the conventional sense. The "training" would be more akin to assay development and validation using various known samples.
9. How the Ground Truth for the Training Set Was Established
Since a "training set" for a machine learning algorithm is not explicitly defined or used in the context of this traditional IVD assay, the method for establishing its ground truth is not applicable in the same way. The development of the assay would have relied on known positive and negative controls, synthetic DNA, and clinical samples with previously determined genotypes (likely via Sanger sequencing or other established reference methods during the predicate device's development or the assay's R&D phase). This type of information is generally part of the assay development and validation process rather than a separate "training set" section in a 510(k) summary.
§ 864.7280 Factor V Leiden DNA mutation detection systems.
(a)
Identification. Factor V Leiden deoxyribonucleic acid (DNA) mutation detection systems are devices that consist of different reagents and instruments which include polymerase chain reaction (PCR) primers, hybridization matrices, thermal cyclers, imagers, and software packages. The detection of the Factor V Leiden mutation aids in the diagnosis of patients with suspected thrombophilia.(b)
Classification. Class II (special controls). The special control is FDA's guidance entitled “Class II Special Controls Guidance Document: Factor V Leiden DNA Mutation Detection Systems.” (See § 864.1(d) for the availability of this guidance document.)