(232 days)
The FIDIS™ CONNECTIVE 10* kit is a semi-quantitative homogeneous fluorescentbased microparticles immunoasay using flow cytometry. The test system is used to simultaneously detect the presence of 10 autoantibody specificities: double stranded DNA (dsDNA), SSA (60 kDa and 52 kDa), SSB, Sm, Sm/RNP, Scl70, Jo1, ribosome and centromere. (*Antibodies to dsDNA, Sm, Sm/RNP, SSA, SSB, Scl-70, Jo-1, ribosome and centromere 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 test is for in vitro diagnostic use.
The FIDIS™ CONNECTIVE 10* kit is a semi-quantitative homogeneous fluorescentbased microparticles immunoasay using flow cytometry. The test system is used to simultaneously detect the presence of 10 autoantibody specificities: double stranded DNA (dsDNA), SSA (60 kDa and 52 kDa), SSB, Sm, Sm/RNP, Scl70, Jo1, ribosome and centromere. The kit includes a 96 wells microplate, vials of color-coded microsphere beads coupled with antigens and internal standard beads, sample dilution buffer, calibrator, positive control, negative control, anti-human IgG coupled to phycoerythrin, washing buffer, reconstitution buffer, package insert, microplate assay configuration worksheet, and microplate sealing films. The test is run on the FIDIS™ Instrument and MLX-BOOSTER™ Software, and may be used with the CARIS™ system (diluting and dispensing device).
The Biomedical Diagnostics S.A. (bmd) FIDIS™ CONNECTIVE 10* assay is a semi-quantitative homogeneous fluorescent-based microparticles immunoassay that uses flow cytometry to detect 10 autoantibody specificities. The device's performance was established through analytical performance studies and comparison studies against a predicate device (K053653 FIDIS™ CONNECTIVE 10* system) and manual assay preparation steps.
1. Table of Acceptance Criteria and Reported Device Performance
The document provides acceptance criteria mainly for precision and outlines performance through agreement studies.
Precision Acceptance Criteria and Reported Performance
| Sample range | Acceptance criteria (CV%) | Within-run minimal CV% | Within-run maximal CV% | Between-run minimal CV% | Between-run maximal CV% |
|---|---|---|---|---|---|
| Less than 10 AU/mL or IU/mL | Not determined | 5.9% | 12.8% | 7.4% | 13.6% |
| 10 to 29 AU/mL or IU/mL | CV ≤ 20% | 2.5% | 11.8% | 8.2% | 17.3% |
| 29 to 800 AU/mL or IU/mL | CV ≤ 15% | 2.1% | 12.7% | 4.5% | 14.3% |
Comparison Study with Predicate Device (K053653 FIDIS™ CONNECTIVE 10)*
The acceptance criteria for the comparison study are implicitly that the agreement (Positive Percent Agreement, Negative Percent Agreement, and Overall Agreement) should demonstrate substantial equivalence to the predicate device. While specific percentage targets are not explicitly stated as "acceptance criteria" in the table format, the observed agreement percentages with 95% LCLs are reported and deemed sufficient for substantial equivalence.
| Antigenic Specificity | Positive Percent Agreement (PPA) | Negative Percent Agreement (NPA) | Overall Agreement (OA) | 95% LCL PPA | 95% LCL NPA | 95% LCL OA |
|---|---|---|---|---|---|---|
| dsDNA | 91.84% | 98.51% | 95.69% | 82.29% | 93.11% | 91.15% |
| SSA 60 kDa | 100% | 98.57% | 99.15% | 93.95% | 93.40% | 96.04% |
| SSA 52 kDa | 95.08% | 96.97% | 96.06% | 87.78% | 90.77% | 91.90% |
| SSB | 100% | 97.14% | 97.85% | 87.79% | 91.28% | 93.39% |
| Sm | 95.83% | 97.33% | 96.97% | 81.71% | 91.84% | 92.35% |
| Sm/RNP | 96.88% | 97.44% | 97.27% | 86.02% | 92.15% | 93.10% |
| Scl70 | 96.43% | 97.14% | 96.94% | 84.15% | 91.28% | 92.28% |
| Jo1 | 96.3% | 100% | 98.96% | 83.60% | 95.75% | 95.15% |
| Centromere | 83.33% | 100% | 95.83% | 65.82% | 95.92% | 90.72% |
| Ribosome | 100% | 100% | 100% | 84.67% | 95.75% | 96.62% |
Comparison Study: Manual vs. Automated (CARIS™) Assay Preparation
Similar to the predicate comparison, the acceptance criteria here are also implicit that agreement between manual and automated methods shows substantial equivalence.
| Antigenic Specificity | Positive Percent Agreement (PPA) | Negative Percent Agreement (NPA) | Overall Agreement (OA) | 95% LCL PPA | 95% LCL NPA | 95% LCL OA |
|---|---|---|---|---|---|---|
| dsDNA | 100% | 100% | 100% | 93.27% | 95.75% | 97.36% |
| SSA 60 kDa | 100% | 100% | 100% | 93.12% | 95.69% | 97.31% |
| SSA 52 kDa | 100% | 98.48% | 98.48% | 94.40% | 93.01% | 96.04% |
| SSB | 100% | 100% | 100% | 88.71% | 95.63% | 96.80% |
| Sm | 100% | 95.83% | 96.88% | 88.27% | 89.58% | 92.12% |
| Sm/RNP | 100% | 95.77% | 97.09% | 91.06% | 89.44% | 92.64% |
| Scl70 | 100% | 100% | 100% | 90.19% | 95.69% | 96.96% |
| Jo1 | 100% | 100% | 100% | 89.12% | 95.75% | 96.90% |
| Centromere | 100% | 94.52% | 95.70% | 86.09% | 87.90% | 90.43% |
| Ribosome | 100% | 100% | 100% | 68.77% | 95.69% | 96.13% |
2. Sample Size Used for the Test Set and Data Provenance
-
Precision Study Test Set:
- Within-run: 6 samples (5 for Jo1) tested 10 times in the same run.
- Between-run: 6 samples (5 for Jo1) tested 3 times per run, across 6 runs.
- The document does not specify the country of origin or whether the data was retrospective or prospective for the precision study samples.
-
Comparison Study with Predicate Device Test Set:
- Sample Size: 264 samples.
- Composition: 194 samples positive for one or more parameters, and 70 negative samples (including some with potential biological interferences).
- Data Provenance: The document states "obtained from routine laboratory" for interfering substances study (part of analytical performance) and implies a similar source for the comparison study, but the specific country of origin or retrospective/prospective nature isn't explicitly stated. However, given the manufacturer is based in France, it's plausible the samples originated from Europe.
-
Comparison Study with Automated (CARIS™) system Test Set:
- Sample Size: 264 samples.
- Composition: 194 samples positive for one or more parameters, and 70 negative samples (including some with potential biological interferences).
- Data Provenance: Same as above.
3. Number of Experts Used to Establish Ground Truth for the Test Set and Their Qualifications
The document does not mention the use of human experts to establish ground truth for the test sets. Instead, the "ground truth" for the comparison studies is defined by the results obtained from the predicate device (K053653 FIDIS™ CONNECTIVE 10 system)* or the manual assay preparation steps of the modified device. For the analytical performance (e.g., precision, interfering substances), the "truth" is based on the inherent characteristics of the spiked or characterized samples.
4. Adjudication Method for the Test Set
This type of in-vitro diagnostic device study typically doesn't involve human adjudication in the traditional sense (e.g., for imaging studies). For the comparison studies, discrepancies were handled as follows:
- "All equivocal samples with predicate and modified CONNECTIVE 10* assays are considered negative for the comparison and the evaluation studies."
- For individual specificities, the number of equivocal results is noted (e.g., "There were 3 equivocal results with the assay. For purposes of calculation, these results were considered as negative."). This method effectively converts equivocal results into negative results for agreement calculations.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done, and Effect Size of AI vs. Without AI Assistance
No, a Multi-Reader Multi-Case (MRMC) comparative effectiveness study was not done. This device is an in-vitro diagnostic test system, not an AI-assisted diagnostic tool that human readers would interact with in the context of interpretation. The comparison is between different versions or methods of the assay itself, or against a predicate device.
6. If a Standalone (Algorithm Only Without Human-in-the-Loop Performance) Was Done
The device itself is a standalone in-vitro diagnostic test system. The performance studies evaluate the device's analytical characteristics and its agreement with a predicate device or different operational modes (manual vs. automated sample preparation). There isn't an "algorithm" in the sense of a standalone AI intended to perform diagnostic interpretation; rather, it's a test system that provides semi-quantitative results. The system operates without human interpretive intervention beyond running the assay and reading the numerical output.
7. The Type of Ground Truth Used
The ground truth for the comparison studies was:
- The results generated by the predicate device (K053653 FIDIS™ CONNECTIVE 10 system)* when comparing the modified device to the predicate.
- The results generated by the manual assay preparation steps when comparing the automated (CARIS™) assay preparation to manual preparation.
For the analytical precision and interfering substances studies, the ground truth was based on the known characteristics of the samples (e.g., characterized positive/negative samples, spiked samples, or samples with known interferences). There is no mention of pathology, expert consensus, or outcomes data being directly used as ground truth for these performance evaluations.
8. The Sample Size for the Training Set
The document does not specify a separate "training set" in the context of machine learning or algorithm development. The studies performed are for performance evaluation and comparison studies for a medical device. Therefore, no training set size is reported in the provided text.
9. How the Ground Truth for the Training Set Was Established
As no training set is indicated, this question is not applicable. The device's operational characteristics and comparisons are the focus of performance evaluation, not machine learning model training.
§ 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).