(38 days)
EliA ß2-Glycoprotein I IgA is intended for the in vitro semi-quantitative measurement of IgA antibodies directed to ß2-Glycoprotein I in human serum and plasma (Li-heparin, EDTA) to aid in the diagnosis of antiphospholipid syndrome (APS) as well as thrombotic disorders related to systemic lupus erythematosus (SLE) in conjunction with other laboratory and clinical findings. EliA B2-Glycoprotein I IgA uses the EliA IgA method on the instrument Phadia 2500/5000.
EliA Cardiolipin IgA is intended for the in vitro sem-quantitative measurement of IgA antibodies directed to cardiolipin in human serum and plasma (Li-heparin, EDTA) to aid in the diagnosis of antiphospholipid syndrome (APS) as well as thrombotic disorders related to systemic lupus erythematosus (SLE) in conjunction with other laboratory and clinical findings. EliA Cardiolipin IgA uses the EliA IgA method on the instrument Phadia 2500/5000.
The method-specific reagents are identical with K112414 (EliA B2-Glycoprotein I IqA) and K131821 (EliA Cardiolipin IqA), but are filled in containers specific for the Phadia 2500/5000 instrument. Each device consists of:
-Test Wells: EliA ß2-Glycoprotein I IqA Wells are coated with human ß2-Glycoprotein I antigen - 2 carriers (12 wells each), ready to use;
- EliA Cardiolipin IgA Wells are coated with bovine cardiolipin antigen and boyine ß2-glycoprotein I as co-factor - 2 carriers (12 wells each), ready to use;
- -EliA Sample Diluent: PBS containing BSA, detergent and 0.095% (w/v) sodium azide - 6 bottles, 48 mL each, ready to use; or 6 bottles, 400 mL each, ready to use;
- -EliA IqA Conjuqate 50 or 200: ß-Galactosidase labeled anti-IgA (mouse monoclonal antibodies) in PBS containing BSA and 0.06% (w/v) sodium azide -6 wedge shaped bottles, 5 mL each, ready to use; or 6 wedge shaped bottles, 19 mL each, ready to use
- EliA IgA Calibrator Strips: Human IgA (0, 0.3, 1.5, 5, 15, 80 µg/L) in PBS containing BSA, detergent and 0.095% (w/v) sodium azide - 5 strips, 6 singleuse vials per strip, 0.3 mL each, ready to use;
- -EliA IgA Curve Control Strips: Human IgA (20 µg/L) in PBS containing BSA, detergent and 0.095% (w/v) sodium azide – 5 strips, 6 single-use vials per strip, 0.3 mL each, ready to use;
- -EliA IgA Calibrator Well: Coated with mouse monoclonal antibodies - 4 carriers (12 wells each), ready to use,
The Phadia EliA Immunodiagnostic System is an automated system for immunodiagnostic testing. The EliA reagents are available as modular packages, each purchased separately. All packages are required to carry out EliA ß2-Glycoprotein I IgA and EliA Cardiolipin IgA tests.
Here's a breakdown of the acceptance criteria and study particulars for the EliA Beta2-Glycoprotein I IgA and EliA Cardiolipin IgA Immunoassays on the Phadia 2500/5000 instrument, based on the provided FDA 510(k) summary (K181329):
1. Table of Acceptance Criteria and Reported Device Performance
The acceptance criteria provided in the document are primarily for method comparison (regression analysis against the predicate device/instrument) and for the performance metrics of Positive Percent Agreement (PPA), Negative Percent Agreement (NPA), and Total Percent Agreement (TPA) when comparing the new instrument platforms (Phadia 2500/5000) to the predicate Phadia 250.
EliA ß2-Glycoprotein I IgA on Phadia 2500/5000
| Performance Metric | Acceptance Criteria (Implicit from approval) | Reported Device Performance (Worst Case Across 3 Instruments) |
|---|---|---|
| Method Comparison (vs. Phadia 250) | ||
| Slope | 0.9 - 1.1 | 0.98 - 1.02 |
| Intercept | Close to 0 | 0.22 - 0.85 |
| PPA (Equivocal considered Positive) | (Not explicitly stated, but high agreement expected) | 97.3% (90.6% – 99.7% CI) |
| NPA (Equivocal considered Positive) | (Not explicitly stated, but high agreement expected) | 80.0% (59.3% – 93.2% CI) |
| TPA (Equivocal considered Positive) | (Not explicitly stated, but high agreement expected) | 94.0% (87.4% – 97.8% CI) |
| PPA (Equivocal considered Negative) | (Not explicitly stated, but high agreement expected) | 100.0% (94.2% – 100% CI) |
| NPA (Equivocal considered Negative) | (Not explicitly stated, but high agreement expected) | 94.6% (81.8% – 99.3% CI) |
| TPA (Equivocal considered Negative) | (Not explicitly stated, but high agreement expected) | 98.0% (93.0% – 99.8% CI) |
| Precision | (Target uncertainty goal for LoQ: 20%; Implicitly, low %CV across runs/instruments) | Total CVs: Up to 26.2% for low conc., 6.6-9.7% for higher conc. |
| Linearity (R²) | Close to 1.00 (e.g., 0.99-1.00) | 1.00 |
| Limit of Detection (LoD) | (Implicitly, as low as possible for clinical utility) | 0.3 EliA U/mL |
| Limit of Quantitation (LoQ) | (Target uncertainty goal of 20%) | 1.1 EliA U/mL |
EliA Cardiolipin IgA on Phadia 2500/5000
| Performance Metric | Acceptance Criteria (Implicit from approval) | Reported Device Performance (Worst Case Across 3 Instruments) |
|---|---|---|
| Method Comparison (vs. Phadia 250) | ||
| Slope | 0.9 - 1.1 | 0.98 - 1.06 |
| Intercept | Close to 0 | -0.40 - 0.30 |
| PPA (Equivocal considered Positive) | (Not explicitly stated, but high agreement expected) | 100.0% (93.8% – 100% CI) |
| NPA (Equivocal considered Positive) | (Not explicitly stated, but high agreement expected) | 88.4% (74.9% – 96.1% CI) |
| TPA (Equivocal considered Positive) | (Not explicitly stated, but high agreement expected) | 95.0% (88.8% – 98.4% CI) |
| PPA (Equivocal considered Negative) | (Not explicitly stated, but high agreement expected) | 93.3% (81.7% – 98.6% CI) |
| NPA (Equivocal considered Negative) | (Not explicitly stated, but high agreement expected) | 94.6% (85.1% – 98.9% CI) |
| TPA (Equivocal considered Negative) | (Not explicitly stated, but high agreement expected) | 94.1% (87.5% – 97.8% CI) |
| Precision | (Target uncertainty goal for LoQ: 20%; Implicitly, low %CV across runs/instruments) | Total CVs: Up to 18.5% for low conc., 6.2-11.9% for higher conc. |
| Linearity (R²) | Close to 1.00 (e.g., 0.99-1.00) | 1.00 |
| Limit of Detection (LoD) | (Implicitly, as low as possible for clinical utility) | 0.3 APL-U/mL |
| Limit of Quantitation (LoQ) | (Target uncertainty goal of 20%) | 1.0 APL-U/mL |
Note: The document primarily outlines how the studies were performed and what the results were, rather than explicit pre-defined quantitative acceptance criteria for all metrics. For method comparison, it states: "The acceptance criteria for the method comparison (the slope for the regression lines should be 0.9 - 1.1 for single replicate to single replicate and intercept close to 0) were met." For LoQ, it mentions "a target uncertainty goal of 20%." For PPA/NPA/TPA, the high reported values and FDA clearance imply acceptance.
2. Sample Size and Data Provenance for Test Set
-
Method Comparison (Instrument Comparison):
- Sample Size: More than 100 serum samples (for each immunoassay).
- Data Provenance: Not explicitly stated, but serum samples were used. It is implied to be from patient populations relevant to the intended use. The samples included "≥20% of the samples within ±25% of the medical decision point," suggesting a distribution covering diagnostically relevant ranges.
- Retrospective/Prospective: Not specified, but typically such comparison studies use retrospectively collected samples for method validation.
-
Precision/Reproducibility:
- Sample Size: 5 serum samples. Each sample tested in 21 runs (3 instruments x 7 runs) with 4 replicates per run, totaling 84 replicates per serum sample.
- Data Provenance: Serum samples. Country of origin not specified.
- Retrospective/Prospective: Retrospective, as these are pre-collected serum samples.
-
Linearity/Assay Reportable Range:
- Sample Size: 4 patient serum samples.
- Data Provenance: Patient serum samples. Country of origin not specified.
- Retrospective/Prospective: Retrospective.
-
Detection Limit (LoB, LoD, LoQ):
- Sample Size:
- LoB: One blank sample measured in 33 replicates in each of two runs.
- LoD & LoQ: Three low-level serum samples measured in 11 replicates in each of two runs.
- Data Provenance: Blank samples and low-level serum samples. Country of origin not specified.
- Retrospective/Prospective: Retrospective.
- Sample Size:
3. Number of Experts and Qualifications for Ground Truth for the Test Set
- This device is an in-vitro diagnostic (IVD) immunoassay, not an AI or imaging device requiring human expert adjudication for ground truth. The "ground truth" for these studies refers to the reference method's result (e.g., predicate device Phadia 250 for method comparison) or the known characteristics of the samples (e.g., spiking for linearity, known concentration for precision controls).
- Therefore, the concept of "number of experts" or their "qualifications" for establishing ground truth in the context of an IVD assay's analytical performance studies is not applicable here.
4. Adjudication Method for the Test Set
- Not applicable as this is an IVD immunoassay, not an AI or imaging device requiring human subjective interpretation and adjudication. The "adjudication" is based on instrumental readings and comparison to defined calibrators and predicate device results.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
- No, an MRMC comparative effectiveness study was not done. This is an IVD immunoassay, not a device that involves human "readers" interpreting cases in the context of medical imaging or clinical decision-making with or without AI assistance.
- The study involved comparing instrumental results of the new Phadia 2500/5000 platform to the predicate Phadia 250 platform.
6. Standalone Performance Study
- Yes, standalone performance studies were done. The precision, linearity, and detection limit studies are examples of standalone performance evaluations of the EliA immunoassays on the Phadia 2500/5000 instrument.
- The primary scope of this 510(k) submission was to introduce these previously cleared assays onto a new instrument platform (Phadia 2500/5000), meaning the "algorithm" (assay chemistry and measurement principle) itself was already established as effective and safe. The studies here demonstrate that this established assay performs equivalently on the new instrument.
7. Type of Ground Truth Used
- Method Comparison: The predicate device's results (EliA ß2-Glycoprotein I IgA on Phadia 250 instrument, K112414; EliA Cardiolipin IgA on Phadia 250 instrument, K131821) served as the "ground truth" or reference for assessing equivalence of the new instrument platform.
- Precision and Linearity: The values obtained from the predicate device or a well-characterized reference are used to establish control ranges and expected values. For linearity, known dilutions are used against expected concentrations.
- Detection Limit: Controlled blank samples and low-level spiked/characterized samples are used.
- Clinical Studies (reference): For clinical utility and cut-off determination mentioned as reviewed in K112414 and K131821, the ground truth would have been clinical diagnosis (e.g., confirmed APS or SLE) and outcomes data. This summary itself does not include new clinical ground truth studies for K181329.
8. Sample Size for the Training Set
- This type of submission (510(k) for a new instrument platform for existing assays) generally does not involve a "training set" in the context of machine learning or AI.
- For IVD assays, optimization and method development would involve numerous samples, but these are part of product development rather than a formal "training set" that would be distinct from a "test set" in the way AI/ML studies define them. The stability and calibration curves are established using a series of known calibrators and controls.
9. How the Ground Truth for the Training Set Was Established
- Not applicable in the AI/ML sense. For standard IVD assay development, ground truth for calibrators and controls is established through rigorous characterization, often against international reference materials or highly purified substances, and validated using established analytical methods and statistical approaches. The clinical cut-offs were derived from "clinical studies (s. K112414 and K131821)", meaning the previous submissions involved clinical data and patient diagnoses to define the clinically relevant ranges.
§ 866.5660 Multiple autoantibodies immunological test system.
(a)
Identification. A multiple autoantibodies immunological test system is a device that consists of the reagents used to measure by immunochemical techniques the autoantibodies (antibodies produced against the body's own tissues) in serum and other body fluids. Measurement of multiple autoantibodies aids in the diagnosis of autoimmune disorders (disease produced when the body's own tissues are injured by autoantibodies).(b)
Classification. Class II (performance standards).