(381 days)
The HYDRASHIFT 2/4 isatuximab kit is intended for the qualitative detection of monoclonal proteins in human serum by immunofixation electrophoresis. The HYDRASHIFT 2/4 isatuximab kit is to be used in conjunction with the HYDRAGEL IF kit and the semi-automated HYDRASYS 2 electrophoresis apparatus. The electropherograms are evaluated visually for the presence of specific reactions with the suspect monoclonal proteins. The HYDRASHIFT 2/4 isatuximab kit removes isatuximab IgG kappa interference and enables the visual evaluation of the presence of monoclonal proteins on HYDRAGEL IF kits in patients who have received isatuximab therapy.
For In Vitro Diagnostic use. For Prescription Use Only.
HYDRASYS 2 is a semi-automated multi-parameter system for start-to finish agarose gel electrophoresis: application of samples, migration, drying, staining, destaining and final-stage drying.
Abnormal bands in serum protein electrophoregrams, primarily those in the beta globulin and gamma globulin zones, are always suspected to be monoclonal proteins (M-proteins, paraproteins, monoclonal immunoqlobulins) and therefore, an indication of performing an Immunofixation technique to type and confirm the monoclonal gammopathies.
lsatuximab is a human therapeutic IgG kappa monoclonal antibody and as such, during the clinical monitoring of patients treated with isatuximab, this antibody simulates a band detected by serum protein electrophoresis and immunofixation in the gamma region. It can simulate an endogenous IgG kappa paraprotein.
The HYDRASHIFT isatuximab immunofixation procedure, performed on the HYDRAGEL IF 2/4 gel, is based on the creation of an isatuximab / anti-isatuximab antibody complex and shifting it outside the gammaglobulins zone. With the HYDRASHIFT isatuximab procedure, the isatuximab / anti-isatuximab antibody complex is visualized in alpha-1 zone on IgG and Kappa immunofixation tracks and then the interference is removed from the gamma zone.
The provided text describes the performance data for the HYDRASHIFT 2/4 isatuximab kit, which is intended for the qualitative detection of monoclonal proteins in human serum by immunofixation electrophoresis, specifically by removing isatuximab IgG kappa interference.
Here's an analysis of the acceptance criteria and study proving the device meets them, based on the provided document:
Acceptance Criteria and Reported Device Performance
The core acceptance criterion for this device, based on the performance data presented, is 100% concordance in visual evaluation of the presence or absence of monoclonal proteins, particularly after the removal of isatuximab interference.
| Acceptance Criteria (Inferred from Performance Goals) | Reported Device Performance |
|---|---|
| Repeatability: Consistent visual evaluation of monoclonal proteins within the same gel and consistent removal of isatuximab interference. | 100% concordant results for all tested samples across 4 runs within the same gel. |
| Reproducibility (between gels, lots, instruments): Consistent visual evaluation of monoclonal proteins and consistent removal of isatuximab interference across different gels, kits from different lots, and different instruments over multiple days. Consistency in characterization (normal or abnormal with monoclonal components) should be maintained. | 100% concordant results for all tested samples across 9 runs (3 gels/day x 3 days) on 3 different instruments and with 3 different kit lots. |
| Comparative Studies (Internal & External): The device must effectively remove isatuximab interference while accurately characterizing normal and pathological serum samples, demonstrating 100% agreement between the standard procedure and the HYDRASHIFT procedure for the characterization of monoclonal proteins in both spiked and native samples, and in samples where isatuximab interference is present or absent. The device should allow for clear visualization and characterization of monoclonal proteins after interference removal. | Internal Study (53 samples): 100% complete agreement between native and isatuximab-spiked samples for 26 normal and 27 pathological serum samples. Monoclonal proteins were detected and characterized with 100% concordance. |
| External Study No. 1 (204 samples): 100% concordant results for 69 normal serum samples and 135 pathological serum samples between the HYDRAGEL 4 IF Acid Violet Dynamic Mask kit and the HYDRASHIFT 2/4 isatuximab procedure. The kit successfully shifted isatuximab in 90 samples where it was visualized. | |
| External Study No. 2 (203 samples): 100% concordant results for 68 normal serum samples and 135 pathological serum samples between the HYDRAGEL 4 IF Acid Violet Standard Mask kit and the HYDRASHIFT 2/4 isatuximab procedure. The kit successfully shifted isatuximab in 90 samples where it was visualized. | |
| Sensitivity (Detection Limit of Isatuximab Interference): The device should effectively handle isatuximab interference at relevant clinical concentrations. | The detection limit of isatuximab and/or isatuximab/anti-isatuximab antibody complex visualized is 0.3 g/L. |
| Interference: The device results should not be affected by common endogenous interfering factors or specific drugs relevant to the patient population. | No interference detected due to specified concentrations of unconjugated bilirubin, conjugated bilirubin, triglycerides, hemoglobin, rheumatoid factor, Human Anti-Mouse Antibody (HAMA), and various chemotherapy drugs (Pomalidomide, Carfilzomib, Dexamethasone, Ixazomib, Cyclophosphamide, Melphalan, Prednisone, Lenalidomide, Bortezomib). |
Study Details Proving Device Meets Acceptance Criteria
1. A table of acceptance criteria and the reported device performance:
(See table above)
2. Sample sizes used for the test set and the data provenance:
- Repeatability Study: 10 different serum samples (2 controls, 8 spiked with monoclonal components). 4 runs per sample within the same gel.
- Reproducibility Study: 8 different serum samples with monoclonal components + Normal Control Serum + Isatuximab Control. Each sample analyzed on 9 runs (1 analysis per gel, over 3 working days) on 3 HYDRASYS 2 instruments with 3 lots of HYDRASHIFT 2/4 isatuximab kit.
- Comparative Studies:
- Internal Study: 53 serum samples (26 normal, 27 pathological).
- External Study No. 1: 204 serum samples.
- External Study No. 2: 203 serum samples. (Note: "The same serum samples were analyzed in both external studies with exception of one sample included in external study 1." suggesting ~204 unique samples across external studies.)
Data Provenance:
- Internal Study: Conducted by Sebia (manufacturer).
- External Studies: Performed in the USA.
- Retrospective/Prospective: Not explicitly stated, but the description of "serum samples" and "analyzed with" suggests they were existing or collected samples, making it likely retrospective for the comparative studies. The repeatability and reproducibility studies appear to be prospective experimental designs.
3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts:
The document does not specify the number or qualifications of experts used to establish the ground truth. The results are described as "100% concordant" based on detection and characterization of monoclonal proteins, which implies a pre-established or expert-verified classification for each sample. However, the exact process or personnel involved in this ground truth establishment are not detailed. Given it's an in vitro diagnostic (IVD) device for lab use, the "ground truth" would likely be the result of a reference method interpretation by qualified lab personnel.
4. Adjudication method (e.g., 2+1, 3+1, none) for the test set:
The document does not specify any adjudication method. The outcome measures are presented as "100% concordant results," which suggests a clear, unambiguous read for each test, or that any discrepancies were resolved, though the process for resolution is not described.
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 study was performed or described. This device is an in vitro diagnostic (IVD) kit for immunofixation electrophoresis, not an AI-assisted diagnostic imaging device for human readers. It automates a lab procedure and provides an electropherogram for visual evaluation. The "visual evaluation" mentioned refers to lab personnel interpreting the results of the gel electrophoresis.
6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done:
Yes, effectively. This device is an IVD kit. Its performance is evaluated on its ability to process serum samples and produce an electropherogram that then is visually evaluated. The "performance data" sections (repeatability, reproducibility, comparative studies) essentially describe the standalone performance of the kit itself in consistently producing the expected analytical result (i.e., shifting the isatuximab band and allowing for accurate detection/characterization of monoclonal proteins). While the final "reading" is visual, the kit's function is mechanistic/chemical, not algorithmic interpretation requiring human oversight in the AI sense.
7. The type of ground truth used (expert consensus, pathology, outcomes data, etc.):
The ground truth appears to be based on the presence and characterization of monoclonal proteins in serum samples, determined by standard laboratory methods and potentially confirmed by expert consensus in a clinical laboratory setting. For the comparative studies, samples were characterized as "normal" or "abnormal with monoclonal components," implying a reference standard or pre-established truth for each sample type. The "native" samples and "spiked" samples with isatuximab served as a form of ground truth for evaluating the device's ability to differentiate between intrinsic monoclonal proteins and isatuximab interference.
8. The sample size for the training set:
Not applicable/Not specified. This is an in vitro diagnostic (IVD) kit, not a machine learning or AI-based device that typically requires a separate "training set" for model development. The development process for such a kit involves chemical and biochemical optimization rather than data-driven learning.
9. How the ground truth for the training set was established:
As above, not applicable. The device is a wet-lab kit, not an AI algorithm.
§ 866.5510 Immunoglobulins A, G, M, D, and E immunological test system.
(a)
Identification. An immunoglobulins A, G, M, D, and E immunological test system is a device that consists of the reagents used to measure by immunochemical techniques the immunoglobulins A, G, M, D, an E (serum antibodies) in serum. Measurement of these immunoglobulins aids in the diagnosis of abnormal protein metabolism and the body's lack of ability to resist infectious agents.(b)
Classification. Class II (performance standards).