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

Anti-MCV® is an indirect solid phase enzyme immunoassay (ELISA) for the qualitative and semi-quantitative measurement of IgG class autoantibodies against mutated citrullinated vimentin (MCV) in human serum. The assay is intended for in vitro diagnostic use only as an aid in the diagnosis of Rheumatoid Arthritis (RA) in conjunction with other laboratory and clinical findings.

Device Description

AI/ML Overview

Here's a breakdown of the acceptance criteria and the study details for the ORGENTEC Anti-Mutated Citrullinated Vimentin IgG EIA, based on the provided text:

Acceptance Criteria and Device Performance

The acceptance criteria for substantial equivalence are primarily demonstrated through comparison with a predicate device (Immunoscan RA anti-CCP Test Kit) and through clinical performance metrics (sensitivity and specificity) against a clinical diagnosis.

Acceptance Criteria Category	Metric/Threshold	Reported Device Performance (ORGENTEC Anti-MCV® EIA)
Method Comparison	Positive Percent Agreement	96.3% (C.I. 95% = 93.0 - 98.3%)
(vs Predicate Device)	Negative Percent Agreement	96.8% (C.I. 95% = 94.2 - 98.5%)
	Overall Agreement	96.6% (C.I. 95% = 94.7 - 97.9%)
Clinical Diagnostic	Clinical Sensitivity (for Rheumatoid Arthritis)	81.2% (C.I. 95% = 77.8 - 84.7%)
Performance	Clinical Specificity (for Rheumatoid Arthritis)	98.0% (C.I. 95% = 96.7 - 98.9%)
	Clinical Agreement (for Rheumatoid Arthritis)	91.5% (C.I. 95% = 89.7 - 92.9%)
Analytical Performance	Intra-Assay reproducibility (CV%)	Ranged from 1.5% to 7.4% (for 16-20 replicates)
	Inter-Assay reproducibility (CV%)	Ranged from 4.6% to 15.3% (for 5 replicates)
	Inter-Lot reproducibility (CV%)	Ranged from 1.5% to 18.4% (for 3 lots)
	Inter-Laboratory precision (CV%)	Ranged from 2.3% to 14.9% (for 3 labs, 22 samples)
	Linearity (Reportable Range)	3.0 to 900 U/mL (R² 0.9963-0.9999, Recovery 81-109%)
	Assay Cut-off for Positivity	> 20 U/mL
	Interference (Bilirubin, Hemolysis, Lipemia)	No interference up to 40 mg/dL, 1000 mg/dL, 3000 mg/dL respectively
	Cross-reactivity (Non-RA Conditions)	1.9% overall positive (ranged per condition)

Study Details

2. Sample sizes used for the test set and the data provenance

Method Comparison Test Set (vs. Predicate Device):
- Sample Size: 555 sera
- Data Provenance: Not explicitly stated as retrospective or prospective, but samples were a mix of "clinically diagnosed Rheumatoid Arthritis disease state samples" and a "presumed normal asymptomatic blood bank population plus other arthritic and autoimmune patient samples obtained from hospital labs and autoimmune clinics." This suggests a retrospective collection of existing samples.
Clinical Diagnostic Performance Test Set:
- Total Sample Size:
  - Rheumatoid Arthritis (RA) Diagnosed Samples: 490 (124 males, 366 females; age 19-92 years)
  - "Presumed Normal" (Specificity) Samples: 234 (from blood donor centers, age 24-82 years)
  - Other Arthritic and Autoimmune Disease Conditions (Specificity) Samples: 522 (from hospitals and autoimmune clinics, age 2-92 years)
- Data Provenance: Similar to the method comparison, the description "obtained from blood donor centers" and "obtained from a variety of clinical sources (hospitals and autoimmune clinics)" suggests a retrospective collection of samples. The countries of origin are not specified but likely include Germany (manufacturer's location).

3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts

The ground truth for the clinical diagnostic performance was established based on "clinically diagnosed patients as having Rheumatoid Arthritis disease" and "presumed normal" individuals. For other conditions, it was "patient samples from other potentially cross-reacting and similar symptoms to Rheumatoid Arthritis."
Number of Experts: Not specified.
Qualifications of Experts: Not specified beyond clinical diagnosis. It can be inferred that these diagnoses were made by medical professionals (e.g., rheumatologists) based on standard clinical practice and criteria (e.g., ACR criteria mentioned generally for RA diagnosis).

4. Adjudication method for the test set

The text does not describe a formal adjudication method (e.g., 2+1, 3+1). The ground truth appears to be based on the existing clinical diagnosis of the patient samples obtained from clinical sources.

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

No MRMC comparative effectiveness study was done or reported. This device is an in-vitro diagnostic (ELISA test), which is an automated assay, not a medical imaging or interpretation device that would typically involve human "readers" in the same way clinical diagnostic AI might.

6. If a standalone (i.e., algorithm only without human-in-the-loop performance) was done

Yes, this is a standalone device. The ORGENTEC Anti-MCV® EIA is an enzyme immunoassay designed for direct measurement of autoantibodies in human serum. Its performance is reported intrinsically, independent of human interpretation other than following the assay protocol and reading the quantitative results. The results are then used as an aid in diagnosis in conjunction with other laboratory and clinical findings, indicating a human physician integrates the results.

7. The type of ground truth used (expert consensus, pathology, outcomes data, etc.)

The ground truth for the clinical studies was based on clinical diagnosis of Rheumatoid Arthritis derived from "clinically diagnosed patients" and "presumed normal" individuals. For specificity, "other arthritic and autoimmune disease conditions" were also used. This implies diagnosis by medical professionals based on established diagnostic criteria, without explicitly stating "expert consensus" or "pathology" as the direct ground truth for each case. For comparison studies, the predicate device results were used as a comparative measure.

8. The sample size for the training set

The documentation does not explicitly mention a "training set" in the context of an algorithm or AI model development. This is an ELISA kit, for which "training set" typically refers to internal development and optimization panels, not a dataset for an AI algorithm. The closest equivalent would be the development of the assay's cut-off and performance characteristics based on various sample populations (e.g., 209 assumed normal blood donor samples for cut-off determination).

9. How the ground truth for the training set was established

As above, there is no explicit "training set" in the AI sense. However, for establishing the normal range and cut-off for the assay, 209 "assumed normal blood donor samples" were used. The ground truth for these samples was their classification as "assumed normal," which is a form of clinical classification based on health status. The cut-off of > 20 U/mL was determined based on the mean + 3 Standard Deviations of these normal samples, aiming for a high specificity (99.5% for normals) at that threshold.

Summary

Regulation Number and Section

§ 866.5775 Rheumatoid factor immunological test system.

(a)
Identification. A rheumatoid factor immunological test system is a device that consists of the reagents used to measure by immunochemical techniques the rheumatoid factor (antibodies to immunoglobulins) in serum, other body fluids, and tissues. Measurement of rheumatoid factor may aid in the diagnosis of rheumatoid arthritis.(b)
Classification. Class II (performance standards).