(174 days)
The HYDRASHIFT 2/4 daratumumab test is intended for the qualitative detection of monoclonal proteins in human serum by immunofixation electrophoresis. The kits are to be used in conjunction with the HYDRAGEL IF kits and the semi-automated HYDRASYS 2 electrophoresis apparatus. The proteins, separated by electrophoresis on alkaline buffered agarose gels, are incubated with individual antisera that are specific against gamma (Ig G), alpha (Ig M) heavy chains, and kappa (free and bound) and lambda (free and bound) light chains, respectively. After removing the nonreacted proteins, the immunoprecipitates are stained with acid violet. The electrophoregrams are evaluated visually for the presence of specific reactions with the suspect monoclonal proteins. The HYDRASHIFT 2/4 daratumumab kits remove the daratumumab Ig G, Kappa interference and enable the visual evaluation of the presence of monoclonal proteins on the HYDRAGEL IF kits in patients who have received daratumumab therapy. For In Vitro Diagnostic Prescription Use Only.
The daratumumab Control is designed for quality control of the HYDRASHIFT daratumumab immunofixation procedure performed using the HYDRASYS 2 instrument. The daratumumab Control is designed for laboratory use. It should be used like a human serum. For In Vitro Diagnostic 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 immunoglobulins) and therefore, an indication of performing an Immunofixation technique to type and confirm the monoclonal gammopathies.
Daratumumab is a human therapeutic Ig G Kappa monoclonal antibody and as such, during the clinical monitoring of patients treated with daratumumab, this antibody simulates a band detected by serum protein electrophoresis and immunofixation in the gamma region. It can simulate an endogenous Ig G Kappa paraprotein.
Daratumumab CONTROL is a qualitative quality control for the assay.
The HYDRASHIFT daratumumab immunofixation procedure performed on HYDRAGEL IF 2/4 gel is based on the creation of a daratumumab / anti-daratumumab antibody complex and shifting it outside the gammaglobulins zone. With the HYDRASHIFT daratumumab procedure, the daratumumab / anti-daratumumab antibody complex is visualized in alpha-1 zone on Ig G and Kappa immunofixation tracks and then the interference is removed from the gamma zone.
The HYDRASHIFT 2/4 daratumumab device is an immunofixation electrophoresis kit designed to remove daratumumab Ig G, Kappa interference, allowing for the visual evaluation of monoclonal proteins in human serum from patients treated with daratumumab. The study to prove the device meets acceptance criteria involved repeatability, reproducibility, and external comparative studies.
1. Table of Acceptance Criteria and Reported Device Performance
| Acceptance Criteria | Reported Device Performance |
|---|---|
| Repeatability (Within-gel concordance) | 100% concordant results for all 10 serum samples (1 normal, 9 with monoclonal components) run 4 times within the same gel. |
| Reproducibility (Between gels, lots, and instruments concordance) | 100% concordant results for all 10 serum samples across 3 instruments, 3 lots, and spanning 3 working days. |
| External Comparative Study 1 Concordance (with/without HYDRASHIFT) | 100% concordant results for 42 normal serum samples and 156 pathological serum samples when comparing results from HYDRAGEL 4 IF alone and HYDRASHIFT 2/4 daratumumab + HYDRAGEL 4 IF. |
| External Comparative Study 2 Concordance (with/without HYDRASHIFT) | 100% concordant results for 38 normal serum samples and 134 pathological serum samples when comparing results from HYDRAGEL 4 IF alone and HYDRASHIFT 2/4 daratumumab + HYDRAGEL 4 IF. |
| Sensitivity (Detection limit of daratumumab/anti-daratumumab antibody complex) | 0.3 q/L |
| Interference (with common interfering factors and drugs) | No interference detected with bilirubin (20 mg/dL), triglycerides (3.00 g/dL), hemoglobin (2 g/L), rheumatoid factor (2000 UI/mL), HAMA (Titer: 640), Pomalidomide (1 mg/L), Lenalidomide (4 mg/L), Dexamethasone (1 mg/L), Bortezomib (2 mg/L). |
2. Sample Sizes Used for the Test Set and Data Provenance
- Repeatability Study: 10 different serum samples (1 normal, 9 with monoclonal components).
- Reproducibility Study: 10 different serum samples (1 normal, 9 with monoclonal components).
- External Comparative Study No. 1: 198 serum samples.
- External Comparative Study No. 2: 172 serum samples (noted that the first 172 samples from study 1 were analyzed on both sites, implying potentially shared samples in part).
The data provenance is from "2 external studies performed in the USA." It is not explicitly stated whether the data was retrospective or prospective.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Their Qualifications
The document does not provide information on the number of experts used or their qualifications for establishing ground truth for the test set. The evaluation of electrophoregrams is noted as "evaluated visually," implying human interpretation, but specifics about the interpreters are absent.
4. Adjudication Method for the Test Set
The document does not explicitly describe an adjudication method (such as 2+1, 3+1) for the test set results. The concordance of results is reported without detailing how disagreements, if any, were resolved.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done, and Effect Size
No MRMC comparative effectiveness study is reported in the provided text. The studies focus on the technical performance of the device (repeatability, reproducibility, and concordance with existing methods) rather than the improvement of human reader performance with or without AI assistance. The device is a "HYDRASHIFT" kit that removes interference for visual evaluation, not an AI-based interpretation system.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done
No standalone algorithm performance study was done. The device is a diagnostic kit that requires visual evaluation of electrophoregrams by a human. Its purpose is to prepare samples to remove interference for human readability, not to interpret the results automatically.
7. The Type of Ground Truth Used
The ground truth appears to be based on the established clinical characterization of the serum samples (e.g., "normal" or "pathological with monoclonal components"). For normal samples, it's the absence of monoclonal components. For pathological samples, it's the specific type of monoclonal component (e.g., Ig G, L + Ig A, K + Ig M, L). This would typically be confirmed by standard laboratory techniques and expert interpretation of immunofixation electrophoresis. The external comparative studies also use existing methods (HYDRAGEL 4 IF alone) as a comparison baseline.
8. The Sample Size for the Training Set
The document does not mention a "training set" as it is typically understood in the context of machine learning or AI. The studies performed are for device validation, focusing on performance characteristics such as repeatability, reproducibility, and comparison with predicate devices, rather than training a model.
9. How the Ground Truth for the Training Set Was Established
Since there is no mention of a training set for an AI/algorithm, there is no information on how its ground truth would have been established. The ground truth for the validation studies (test sets) is based on the known characteristics of the serum samples and comparison with established methods.
§ 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).