(84 days)
The FIDIS™ CONNECTIVE 10* kit is a semi-quantitative homogeneous fluorescent-based microparticles immunoassay using flow cytometry. The test system is used to simultaneously detect the presence of 10 autoantibody specificities: double stranded DNA (dsDNA), SS-A (60kDa and TRIM 21 (SS-A 52kDa)), SS-B, Sm, Sm/RNP, Scl-70, Jo-1, ribosomes and centromere (CENP-B).
(*Antibodies to dsDNA, Sm, Sm/RNP, SS-A, SS-B, Scl-70, Jo-1, ribosomes and CENP-B can be reported using this assay).
Clinical utility:
The results of the FIDIS™ CONNECTIVE 10 are to be used in conjunction with the clinical findings and the other laboratory tests to aid in the diagnosis of connective diseases (systemic lupus erythematosus (SLE), Sjogren's syndrome, mixed connective tissue disease (MCTD), scleroderma, dermatomyositis and CREST syndrome).
FIDIS™ CONNECTIVE 10 kit uses serum only, and is to be run on the FIDIS™ Instrument and MLX-BOOSTER™ Software.
FIDIS™ CONNECTIVE 10 kit may be used with the CARIS™ system (diluting and dispensing device).
This kit is for In vitro diagnostic use.
FIDIS™ CONNECTIVE 10 kit is a multiplex flow immunoassay, which allows simultaneous identification and detection of several antibodies.
FIDIS™ CONNECTIVE 10 is based on the use of distinct uniform size color-coded microsphere sets and a benchtop flow cytometer interfaced to digital signal processing hardware and software. A red diode laser beam in the flow cytometer recognizes each set of microspheres on the basis of its unique fluorescence intensity (red and infrared) thus identifying which parameter is being tested. At the same time, a green laser beam illuminates the external second molecule fluorescence to quantify the reaction related to the specific antigen.
Ten different fluorescently "colored" sets of microspheres are coated with antigens associated with various connective diseases (dsDNA, SS-A (60kDA and TRIM 21 (SS-A 52kDa}}, SS-B, Sm, Sm/RNP, Scl-70, Jo-1, ribosomes and centromere). An additional microsphere (Internal Bead standard) set is coated with anti-IgG to ensure that false negative results due to operational error are detected.
The eleven different sets of microspheres are mixed together. The mixture is lyophilized and constitutes the final microspheres reagent.
The test is performed using a 96 wells microplate with a filtering membrane at the bottom of the wells.
In the first step, the sample is distributed in each well containing the reconstituted microspheres mixture, allowing any anti-dsDNA; anti-SS-A (60kDa and TRIM 21 (SS-A 52kDa)), anti-SS-B, anti-Sm, anti-Sm/RNP, anti-Scl-70, anti-Io-1, anti-ribosomes and anti-centromere antibodies present to bind to the immobilized antigens on the microspheres, as well as free IgG to bind to the anti-IgG microsphere.
After incubation, a wash step using a filtration process removes the unbound antibodies.
A phycoerythrin anti-human IgG conjugate is then added that binds to the previously bound antibodies.
A final wash step stops the reaction and eliminates the unbound conjugate.
The reaction is then measured directly by the flow cytometer, which distinguishes each set of microspheres by its fluorescence color while simultaneously measuring the average fluorescence emitted by the conjugate.
A calibration system allows the determination of the titer (AU/mL) of each sample by interpolation for each antigenic specificity.
Here's a breakdown of the acceptance criteria and the study details for the FIDIS™ CONNECTIVE 10 Assay kit:
1. Table of Acceptance Criteria and Reported Device Performance
The acceptance criteria for the modified FIDIS™ CONNECTIVE 10 assay were based on demonstrating substantial equivalence to the predicate device (K071210). This was primarily assessed through agreement studies, ensuring high Positive Percent Agreement (PPA), Negative Percent Agreement (NPA), and Overall Agreement.
The document reports two main studies:
- Comparison Study with Predicate - Using Manual Pipetting: This compares the modified device against the predicate device.
- Performance Data for Modified FIDIS™ CONNECTIVE 10 with CARIS™ (diluting/dispensing Device): This compares the modified device using automated (CARIS™) versus manual assay preparation steps.
Below is a summary of the reported performance for each antigenic specificity from the "Comparison study with predicate - Using Manual Pipetting" (equivocal results considered negative, as presented in the first set of measures, which typically represents a more conservative approach). Similar performance was observed when equivocal results were considered positive, and across the CARIS™ system comparisons.
| Antigenic Specificity | Acceptance Criteria (Implicit: High Agreement) | Reported Positive Percent Agreement (PPA) | Reported Negative Percent Agreement (NPA) | Reported Overall Agreement |
|---|---|---|---|---|
| dsDNA | High Agreement (vs. Predicate) | 100% | 98.4% | 98.8% |
| SS-A 60kDa | High Agreement (vs. Predicate) | 100% | 98.2% | 98.8% |
| TRIM 21 (SS-A 52kDa) | High Agreement (vs. Predicate) | 95.8% | 100% | 98.8% |
| Sm | High Agreement (vs. Predicate) | 100% | 100% | 100% |
| SS-B | High Agreement (vs. Predicate) | 100% | 98.5% | 98.8% |
| Sm/RNP | High Agreement (vs. Predicate) | 100% | 98.4% | 98.8% |
| Scl-70 | High Agreement (vs. Predicate) | 100% | 96.9% | 97.5% |
| CENP-B | High Agreement (vs. Predicate) | 100% | 98.6% | 98.8% |
| Jo-1 | High Agreement (vs. Predicate) | 100% | 100% | 100% |
| Ribosomes | High Agreement (vs. Predicate) | 100% | 100% | 100% |
Note: The document implicitly defines "high agreement" as meeting the criteria for substantial equivalence to the predicate device. Specific numerical thresholds for agreement were not explicitly stated as acceptance criteria in the document, but the consistent high percentages demonstrate that the device met the expectation for equivalence.
2. Sample Size Used for the Test Set and Data Provenance
- Sample Size for Test Set: 80 samples for each comparison study (77 positive for one or more parameters, 3 negative samples).
- Data Provenance: The document does not explicitly state the country of origin for the samples used in the comparison studies. It also does not specify if the data was retrospective or prospective, though it appears to be retrospective as the samples were "characterized with the predicate test."
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
The document does not mention the use of experts to establish ground truth for the test set. The comparison studies used the results from the predicate device (FIDIS™ CONNECTIVE 10 K071210) as the comparator (reference standard) for calculating agreement.
4. Adjudication Method for the Test Set
There was no human adjudication for the test set. Equivocal results were handled by being considered either negative or positive for calculation purposes, and both scenarios were presented.
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 is an in vitro diagnostic (IVD) assay kit for autoantibody detection, not an AI-assisted diagnostic imaging device that involves human readers.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) was done
This is an in vitro diagnostic immunoassay Kit. The performance described is for the device operating in a standalone manner, providing semi-quantitative results for autoantibodies in serum. There isn't a "human-in-the-loop" component in the interpretation of the assay's direct numerical output, but clinical interpretation of the results in conjunction with other findings is intended. The comparison studies effectively represent standalone performance against a predicate device.
7. The Type of Ground Truth Used
The ground truth for the comparison studies was based on the results obtained from the legally marketed predicate device: FIDIS™ CONNECTIVE 10 (K071210). This implicitly means the predicate device's results were considered the "truth" for the purpose of demonstrating substantial equivalence.
8. The Sample Size for the Training Set
The document does not specify a separate "training set" in the context of an algorithm or AI. For the precision studies, various samples were used to calculate within-run and between-run variability. For the comparison studies, 80 samples were used as the test set to compare the modified device against the predicate. This is a traditional IVD device, not an AI/ML device with distinct training and test sets in the software sense.
9. How the Ground Truth for the Training Set Was Established
Not applicable, as there is no explicitly defined "training set" with a separate ground truth establishment process in the context of this IVD device submission. The performance assessment relies on comparison to a cleared predicate device and internal precision studies.
§ 866.5100 Antinuclear antibody immunological test system.
(a)
Identification. An antinuclear antibody immunological test system is a device that consists of the reagents used to measure by immunochemical techniques the autoimmune antibodies in serum, other body fluids, and tissues that react with cellular nuclear constituents (molecules present in the nucleus of a cell, such as ribonucleic acid, deoxyribonucleic acid, or nuclear proteins). The measurements aid in the diagnosis of systemic lupus erythematosus (a multisystem autoimmune disease in which antibodies attack the victim's own tissues), hepatitis (a liver disease), rheumatoid arthritis, Sjögren's syndrome (arthritis with inflammation of the eye, eyelid, and salivary glands), and systemic sclerosis (chronic hardening and shrinking of many body tissues).(b)
Classification. Class II (performance standards).