FDA 510(k) Search - By Innolitics (SaMD and AI Experts)

EliA RNA Pol III is intended for the in vitro semi-quantitative measurement of IgG antibodies directed to RNA polymerase III (RNA Pol III) in human serum as an aid in the diagnosis of systemic sclerosis (diffuse form) in conjunction with other laboratory and clinical findings. EliA RNA Pol III uses the EliA IgG method.

Device Description

EliA RNA Pol III is a semi-quantitative solid-phase fluoroenzymeimmunoassay, for the determination of autoantibodies against RNA polymerase III. The EliA RNA Pol III test System is fully integrated and automated system which comprises of assay-specific reagents, EliA method-specific reagents, and general reagents.

AI/ML Overview

Here's a breakdown of the acceptance criteria and study information for the EliA RNA Pol III device, based on the provided text:

Acceptance Criteria and Device Performance

Acceptance Criteria Category	Specific Criteria	Reported Device Performance	Comments
Analytical Precision (Phadia 250)	Within-Run %CV	1.7% to 3.8%	Meets precision requirements.
	Between-Run %CV	1.4% to 2.3%	Meets precision requirements.
	Between-Instrument %CV	0.7% to 3.0%	Meets precision requirements.
	Lot-to-Lot %CV	0.5% to 2.2%	Meets precision requirements.
	Total Imprecision %CV	2.9% to 5.3%	Meets precision requirements.
Within-Lab Imprecision (Phadia 250)	Within-Run %CV	2.0% to 2.2%	Meets precision requirements.
	Between-Run %CV	1.4% to 2.6%	Meets precision requirements.
	Between-Day %CV	0.9% to 1.7%	Meets precision requirements.
	Total Within-Lab Imprecision %CV	2.8% to 3.3%	Meets precision requirements.
Analytical Precision (Phadia 2500/5000 E-module)	Within-Run %CV	2.7% to 4.9%	Meets precision requirements.
	Between-Run %CV	0.8% to 2.3%	Meets precision requirements.
	Between-Instrument %CV	2.0% to 5.9%	Meets precision requirements.
	Total Imprecision %CV	4.7% to 6.7%	Meets precision requirements.
Linearity/Assay Reportable Range	R^2 for dilution ranges	1.00 (Phadia 250), 1.00 (Phadia 2500E)	Linearity demonstrated across the entire measuring range.
Hook Effect/Over the Range	Not applicable	Results above upper limit reported as ">192".	No hook effect observed.
Traceability	IgG calibrators traceable to IRP 67/86 of Human Serum Immunoglobulins A, G and M from WHO.	Achieved traceability through comparison to secondary standard or IRP.	Meets traceability requirements.
Stability (Shelf-life)	EliA RNA Pol III Wells stability	18 months at 2-8°C	Meets stability requirements.
Stability (On-board stability)	EliA RNA Pol III carriers stability	28 days at 2-8°C	Meets stability requirements.
Stability (Open Stability)	EliA RNA Pol III wells after opening	9 months at 2-8°C	Meets stability requirements.
Detection Limit (LoB, LoD, LoQ)	LoD/LoQ (target 0.7 EliA U/mL)	LoB: 0.0 U/mL (both instruments); LoD: 0.1-0.2 U/mL; LoQ: 0.3-0.4 U/mL	All results below and in support of the harmonized limits of 0.7 EliA U/mL.
Analytical Specificity (Interference)	Ratio of blank/spiked sample (target 0.94-1.04)	Ranged from 0.94 – 1.04	No interference observed from tested substances up to specified concentrations.
Reference Sera	CDC samples detected according to target values.	All 12 CDC samples detected according to target.	Meets reference sera performance.
Assay Cut-Off (Equivocal results considered negative)	Positive Percent Agreement vs. Predicate Device (QUANTA LITE)	79.2% (95% CI: 65.0 - 89.5)	Comparison to predicate device.
	Negative Percent Agreement vs. Predicate Device (QUANTA LITE)	100% (95% CI: 89.7 - 100)	Comparison to predicate device.
	Total Agreement vs. Predicate Device (QUANTA LITE)	87.8% (95% CI: 78.7 - 94.0)	Comparison to predicate device.
Assay Cut-Off (Equivocal results considered positive)	Positive Percent Agreement vs. Predicate Device (QUANTA LITE)	87.5% (95% CI: 74.8 - 95.3)	Comparison to predicate device.
	Negative Percent Agreement vs. Predicate Device (QUANTA LITE)	100% (95% CI: 89.7 - 100)	Comparison to predicate device.
	Total Agreement vs. Predicate Device (QUANTA LITE)	92.7% (95% CI: 84.8 - 97.3)	Comparison to predicate device.
Clinical Sensitivity (SSc diffuse, equivocal results evaluated as positive)	Sensitivity	25.0% (95% CI: 18.0% - 33.3%)	Specific to diagnosis of systemic sclerosis (diffuse form).
Clinical Specificity (SSc diffuse, equivocal results evaluated as positive)	Specificity	99.1% (95% CI: 97.8% - 99.8%)	Specific to diagnosis of systemic sclerosis (diffuse form).
Clinical Sensitivity (SSc diffuse, equivocal results evaluated as negative)	Sensitivity	22.7% (95% CI: 15.9% – 30.8%)	Specific to diagnosis of systemic sclerosis (diffuse form).
Clinical Specificity (SSc diffuse, equivocal results evaluated as negative)	Specificity	99.6% (95% CI: 98.5% - 99.9%)	Specific to diagnosis of systemic sclerosis (diffuse form).

Study Details

2. Sample Size and Data Provenance for the Test Set:

Test Set (Method Comparison with Predicate Device):
- Sample Size: 193 patient serum samples.
- Data Provenance: Not explicitly stated, but includes 126 samples with a diagnosis of SSc. The context suggests these are clinical samples.
Test Set (Clinical Sensitivity and Specificity):
- Sample Size: 596 clinically defined serum samples.
- Data Provenance: Clinically defined samples from patients with various diagnoses, including Systemic Sclerosis (diffuse and limited forms), and various control diseases/conditions (e.g., Celiac disease, Crohn's disease, SLE, RA, bacterial/viral infections). The text does not specify country of origin or if prospective/retrospective; however, "clinically defined serum samples" typically implies retrospective collection with known diagnoses.
Test Set (Assay Cut-Off):
- Sample Size: 70 apparently healthy blood donor samples and 17 target disease (Systemic Sclerosis, diffuse) samples.
- Data Provenance: "apparently healthy blood donor samples" and "target disease samples" (Systemic Sclerosis, diffuse). The text explicitly mentions "sera from Caucasian, African American, Hispanic and Asian population obtained from a blood bank" for the frequency distribution, which likely overlaps with the "apparently healthy blood donor samples" used for cut-off establishment.

3. Number of Experts and Qualifications for Ground Truth (Test Set):

Number of Experts: Not specified.
Qualifications of Experts: Not specified. The wording "clinically defined serum samples with a diagnosis" implies that the diagnoses used as ground truth were established clinically by medical professionals, but their specific roles, number, or years of experience are not detailed.

4. Adjudication Method (Test Set):

Adjudication Method: Not specified. The diagnostic labels for the clinical samples are presented as established fact without mention of an adjudication process.

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

Was an MRMC study done? No. This device is an in-vitro diagnostic (IVD) assay designed for automated measurement of antibodies, not for interpretation by human readers. Therefore, an MRMC comparative effectiveness study regarding human reader improvement with AI assistance is not applicable.

6. Standalone (Algorithm Only) Performance:

Was a standalone study done? Yes. The entire performance evaluation, including analytical performance, method comparison, and clinical sensitivity/specificity, evaluates the performance of the EliA RNA Pol III assay itself (the "algorithm only" in this context, as it's an automated system) without human interpretation as part of the primary measurement. The results are generated directly by the instrument.

7. Type of Ground Truth Used:

For Method Comparison: The ground truth was the results from the predicate device, QUANTA LITE RNA POL III ELISA.
For Clinical Sensitivity and Specificity: The ground truth was clinical diagnosis ("clinically defined serum samples with a diagnosis from patients with systemic sclerosis, diffuse," etc.).
For Assay Cut-Off: The ground truth was based on apparently healthy blood donors and clinically diagnosed Systemic Sclerosis, diffuse patients.

8. Sample Size for the Training Set:

Training Set (Assay Cut-Off establishment): This involved 70 apparently healthy blood donor samples and 17 target disease (Systemic Sclerosis, diffuse) samples. While not explicitly called a "training set," these samples were used to "define the cut-off," which is a form of model training/optimization for classification.
Other "training" data: The document mentions that "New batches of IgG calibrators are compared to a secondary standard (standardized with the IRP) or the IRP directly and adjusted accordingly to meet the correct concentration." This implies a continuous process of calibration and standardization, where previous data/standards (IRP) could be considered a form of "training" for the calibrators. However, a distinct, large-scale training set for an AI/algorithm in the conventional sense is not detailed as this is a chemical assay.

9. How the Ground Truth for the Training Set was Established:

For Assay Cut-Off establishment: The ground truth for the 70 apparently healthy blood donors means they were confirmed healthy (presumably through standard screening). For the 17 Systemic Sclerosis (diffuse) samples, the ground truth was their clinical diagnosis.
For Calibrators: The ground truth for calibrators is established through their traceability to the International Reference Preparation (IRP) 67/86 of Human Serum Immunoglobulins A, G and M from WHO.

Summary

Regulation Number and Section

§ 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).