(89 days)
EliA PR3s is intended for the in vitro semi-quantitative measurement of IgG antibodies directed to proteinase 3 (PR3) in human serum and plasma (Li-heparin, EDTA) as an aid in the clinical diagnosis of Granulomatosis with Polyangiitis (GPA, formerly called Wegener's Granulomatosis) in conjunction with other laboratory and clinical findings. EliA PR3s uses the EliA IgG method on the instrument Phadia 2500/5000.
EliA MPOs is intended for the in vitro semi-quantitative measurement of IgG antibodies directed to myeloperoxidase (MPO) in human serum and plasma (Li-heparin, EDTA) as an aid in the clinical diagnosis of microscopic polyangiitis (MPA) in conjunction with other laboratory and clinical findings. EliA IgG method on the instrument Phadia 2500/5000.
EliA GBM is intended for the in vitro semi-quantitative measurement of IgG antibodies to a3 chain of collagen IV in human serum and plasma (Li-heparin, EDTA) as an aid in the clinical diagnosis of Goodpasture syndrome in conjunction with other laboratory and clinical findings. EliA GBM uses the EliA IgG method on the instrument Phadia 2500/5000.
The method-specific reagents are identical with K140225, but are filled in containers specific for the Phadia® 2500/5000 instrument. Each device consists of:
- Test Wells: -
EliA PR3S Wells are coated with human PR3 protein – 4 carriers (12 wells each), ready to use:
EliA MPOS Wells are coated with human MPO protein – 4 carriers (12 wells each), ready to use;
EliA GBM Wells are coated with human recombinant α3 chain of collagen IV – 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 IgG Conjugate 50 or 200: ß-Galactosidase labeled anti-IgG (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 IgG Calibrator Strips: Human IgG (0, 4, 10, 20, 100, 600 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 IgG Curve Control Strips: Human IgG (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 IgG Calibrator Well: Coated with mouse monoclonal antibodies 4 carriers (12 wells each), ready to use.
- -EliA ANCA/GBM Positive Control 2500/5000: Human serum containing IgG antibodies to PR3, MPO and GBM in PBS containing BSA, detergent and 0.095% (w/v) sodium azide - 6 single use vials, 0.3 mL each, ready to use;
- -EliA IgG/IqM/IgA Negative Control 2500/5000: Human sera from healthy donors in PBS containing BSA, detergent and 0.095% (w/v) sodium azide -6 single-use vials, 0.3 mL 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. Apart from the EliA ANCA/GBM Positive Control 2500/5000 and the EliA IgG/ IgM/IgA Negative Control 2500/5000, all packages listed above are required to carry out an EliA PR3°, EliA MPOS and EliA GBM tests.
The provided text describes the acceptance criteria and study results for the EliA PR3s, EliA MPOs, and EliA GBM immunoassays when used on the Phadia 2500/5000 instrument. This submission is to add these previously cleared assays to a new instrument platform, so the focus is on method comparison rather than clinical studies.
Here's the breakdown of the requested information:
1. Table of acceptance criteria and reported device performance for Instrument Comparison (Method Comparison):
The acceptance criteria for method comparison (comparing Phadia 2500/5000 to the predicate Phadia 250) were:
- Slope for the regression lines should be between 0.9 and 1.1 for single replicate to single replicate.
- Intercept close to 0.
The performance is reported for each immunoassay (EliA PR3s, EliA MPO®, EliA GBM) and for each of the three Phadia 2500/5000 instruments (A, B, C) tested against the Phadia 250.
EliA PR3s on Phadia 2500/5000 (vs. Phadia 250):
| Instrument | Intercept (95% CI) | Slope (95% CI) | PPA (95% CI) - Equivocal considered Positive | NPA (95% CI) - Equivocal considered Positive | TPA (95% CI) - Equivocal considered Positive | PPA (95% CI) - Equivocal considered Negative | NPA (95% CI) - Equivocal considered Negative | TPA (95% CI) - Equivocal considered Negative |
|---|---|---|---|---|---|---|---|---|
| PH2500/5000 A | 0.15 (-0.07 to 0.33) | 0.99 (0.94 to 1.03) | 98.8% (93.7% - 100%) | 76.5% (50.1% - 93.2%) | 95.1% (89.0% - 98.4%) | 98.6% (92.5% – 100%) | 96.8% (83.3% – 99.9%) | 98.1% (93.2% – 99.8%) |
| PH2500/5000 B | 0.10 (-0.07 to 0.28) | 1.00 (0.96 to 1.04) | 100.0% (95.8% - 100%) | 76.5% (50.1% - 93.2%) | 96.1% (90.4% - 98.9%) | 97.2% (90.3% – 99.7%) | 96.8% (83.3% – 99.9%) | 97.1% (91.7% – 99.4%) |
| PH2500/5000 C | -0.01 (-0.12 to 0.14) | 1.00 (0.96 to 1.04) | 98.8% (93.7% - 100%) | 76.5% (50.1% - 93.2%) | 95.1% (89.0% - 98.4%) | 98.6% (92.5% – 100%) | 93.5% (78.6% – 99.2%) | 97.1% (91.7% – 99.4%) |
EliA MPO® on Phadia 2500/5000 (vs. Phadia 250):
| Instrument | Intercept (95% CI) | Slope (95% CI) | PPA (95% CI) - Equivocal considered Positive | NPA (95% CI) - Equivocal considered Positive | TPA (95% CI) - Equivocal considered Positive | PPA (95% CI) - Equivocal considered Negative | NPA (95% CI) - Equivocal considered Negative | TPA (95% CI) - Equivocal considered Negative |
|---|---|---|---|---|---|---|---|---|
| PH2500/5000 A | -0.02 (-0.27 to 0.09) | 0.98 (0.95 to 1.00) | 97.8% (92.2% - 99.7%) | 87.5% (61.7% – 98.4%) | 96.2% (90.6% - 99.0%) | 97.5% (91.2% – 99.7%) | 100.0% (87.2% – 100%) | 98.1% (93.4% - 99.8%) |
| PH2500/5000 B | -0.02 (-0.24 to 0.10) | 0.98 (0.96 to 1.01) | 98.9% (93.8% – 100%) | 88.2% (63.6% - 98.5%) | 97.1% (91.9% - 99.4%) | 97.4% (90.9% – 99.7%) | 100.0% (87.7% – 100%) | 98.1% (93.3% - 99.8%) |
| PH2500/5000 C | -0.09 (-0.34 to -0.02) | 0.99 (0.96 to 1.02) | 98.9% (93.9% – 100%) | 88.2% (63.6% - 98.5%) | 97.2% (92.0% - 99.4%) | 97.4% (91.0% – 99.7%) | 100.0% (87.7% – 100%) | 98.1% (93.4% - 99.8%) |
EliA GBM on Phadia 2500/5000 (vs. Phadia 250):
| Instrument | Intercept (95% CI) | Slope (95% CI) | PPA (95% CI) - Equivocal considered Positive | NPA (95% CI) - Equivocal considered Positive | TPA (95% CI) - Equivocal considered Positive | PPA (95% CI) - Equivocal considered Negative | NPA (95% CI) - Equivocal considered Negative | TPA (95% CI) - Equivocal considered Negative |
|---|---|---|---|---|---|---|---|---|
| PH2500/5000 A | 0.85 (0.56 to 1.21) | 0.94 (0.92 to 0.96) | 100.0% (95.5% - 100%) | 84.2% (60.4% - 96.6%) | 97.0% (91.5% - 99.4%) | 98.6% (92.6% – 100%) | 92.6% (75.7% – 99.1%) | 97.0% (91.5% – 99.4%) |
| PH2500/5000 B | 1.04 (0.73 to 1.39) | 0.95 (0.91 to 0.99) | 100.0% (95.5% - 100%) | 84.2% (60.4% - 96.6%) | 97.0% (91.4% - 99.4%) | 98.6% (92.5% – 100%) | 92.6% (75.7% – 99.1%) | 97.0% (91.4% – 99.4%) |
| PH2500/5000 C | 0.34 (0.04 to 0.63) | 0.98 (0.95 to 1.00) | 100.0% (95.5% - 100%) | 89.5% (66.9% - 98.7%) | 98.0% (93.0% - 99.8%) | 98.6% (92.6% – 100%) | 100.0% (87.2% – 100%) | 99.0% (94.6% – 100%) |
2. Sample size used for the test set and the data provenance:
- Sample Size: More than 100 samples for each EliA test (PR3s, MPO®, GBM). The submission also specifies "≥20% of the samples within ±25% of the medical decision point."
- Data Provenance: Not explicitly stated as "country of origin," but implies clinical samples used for method comparison. The samples are referred to as "patient serum samples." It is a prospective study as the comparison aims to show equivalence of the new instrument platform with the predicate.
3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts:
This information is not provided in the given text. The study is a method comparison between two instruments (Phadia 250 and Phadia 2500/5000) using the same assays, not a clinical study to establish diagnostic accuracy against a clinical gold standard determined by experts. The "ground truth" for the method comparison is the measurement value obtained from the predicate Phadia 250 instrument.
4. Adjudication method (e.g. 2+1, 3+1, none) for the test set:
This information is not applicable as the study is a method comparison of quantitative measurements, not a diagnostic study requiring expert adjudication of cases. The comparison is based on numerical results from two instruments.
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:
This is not applicable. The device described is an immunoassay system for semi-quantitative measurement of antibodies, not an AI-assisted diagnostic imaging device used by human readers.
6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done:
The device (EliA immunoassays on Phadia 2500/5000) operates as a standalone automated system for measuring antibody levels. The results are semi-quantitative measurements that are an aid in clinical diagnosis, meaning a human clinician interprets the results in conjunction with other findings. However, the performance data presented (precision, linearity, detection limits, method comparison) is reflective of the standalone performance of the algorithm/instrument system. Therefore, the analytical performance studies (precision, linearity, detection limit) and method comparison effectively represent standalone algorithmic performance.
7. The type of ground truth used (expert consensus, pathology, outcomes data, etc.):
For the method comparison study, the "ground truth" for evaluating the performance of the EliA assays on the Phadia 2500/5000 instrument was the results obtained from the predicate device, Phadia 250 instrument.
8. The sample size for the training set:
This information is not applicable as the devices are immunoassays, not machine learning algorithms that require a specific training set in the typical sense. The underlying EliA IgG method and its associated reagents were previously reviewed (K140225), implying that analytical performance of the assay itself was established in prior submissions. This current submission focuses on instrument equivalence.
9. How the ground truth for the training set was established:
This is not applicable for the same reasons as point 8. The assays do not involve machine learning with a distinct training set. The "ground truth" for establishing the analytical parameters and clinical performance of the immunoassays themselves would have been established through extensive analytical validation (e.g., against reference methods, known positive/negative samples, clinical samples with confirmed diagnoses) in their original clearance (K140225).
§ 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).