(30 days)
HYDRASHIFT 2/4 daratumumab kits are to be used in conjunction with the HYDRAGEL IF kits and the semi-automated HYDRASYS 2 electrophoresis apparatus. HYDRASHIFT 2/4 daratumumab with the HYDRAGEL IF kit are intended for the qualitative detection of monoclonal proteins in human serum by immunofixation electrophoresis. The proteins, separated by electrophoresis on alkaline buffered agarose gels, are incubated with individual antisera that are specific against gamma (Ig G), alpha (Ig A) and mu (Ig M) heavy chains, and kappa (free and bound) and lambda (free and bound) light chains, respectively. After removing the non-reacted 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 or absence of monoclonal proteins on the HYDRAGEL IF kits in patients who have received daratumumab therapy.
HYDRASYS 2 is a semi-automated multi-parameter system for start-to finish agarose gel electrophoresis: application of samples, migration, incubation, 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 qammopathies. Daratumumab is a human therapeutic Iq 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. 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 bv electrophoresis on alkaline buffered agarose gels, are incubated with individual antisera that are specific against gamma (lg G), alpha (lg A) and mu (lg M) heavy chains, and kappa (free and bound) and lambda (free and bound) light chains, respectively. After removing the non-reacted 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 lg G, Kappa interference and enable the visual evaluation of the presence or absence of monoclonal proteins on the HYDRAGEL IF kits in patients who have received daratumumab therapy.
The provided FDA 510(k) summary describes the HYDRASHIFT 2/4 daratumumab device, which is an in-vitro diagnostic test. It is a modification of a previously cleared device. The acceptance criteria and study details are primarily focused on demonstrating that the modified device performs equivalently to the predicate device.
Here's an breakdown of the information requested:
1. Table of Acceptance Criteria and Reported Device Performance
The core of the study is a comparison between the modified device (HYDRASHIFT 2/4 daratumumab with anti-daratumumab from Chinese Hamster Ovary cells, referred to as 'Candidate/Modified Device' or 'CHO') and the predicate device (HYDRASHIFT 2/4 daratumumab with anti-daratumumab murine, referred to as 'Predicate Device (K172195)' or 'murine').
| Acceptance Criteria Category | Specific Criteria | Reported Device Performance (Modified Device) |
|---|---|---|
| Intended Use | Must be the same as the predicate device. | Same as the predicate device: Qualitative detection of monoclonal proteins in human serum by immunofixation electrophoresis, removing daratumumab IgG Kappa interference to enable visual evaluation of monoclonal proteins in patients who have received daratumumab therapy. |
| Instrumentation | Must be the same as the predicate device. | Same: Sebia HYDRASYS 2. |
| Immunofixation Test Kits | Must be the same as the predicate device. | Same: HYDRAGEL 4 IF Acid violet Standard mask, HYDRAGEL 4 IF Acid violet Dynamic mask. |
| Scientific Technology | Must be the same as the predicate device. | Same: Agarose Gel Electrophoresis. |
| Specimen Type | Must be the same as the predicate device. | Same: Serum. |
| Results | Must be the same as the predicate device (qualitative). | Same: Qualitative. |
| Sensitivity/Lowest Detectable Daratumumab Limit | The detection limit of daratumumab and/or daratumumab/anti-daratumumab antibody complex visualized should be 0.3 g/L. | The detection limit was visualized at 0.3 g/L, the same as the predicate device. |
| Efficiency (Maximum Removal of Complex) | Should be 3.0 g/L. | The efficiency of the shift of the daratumumab complex to the alpha-1 zone is 3.0 g/L, the same as the predicate device. |
| Daratumumab Band Shift | When HYDRASHIFT treated, daratumumab band should be removed from gamma zone into alpha zone. | Removed from gamma zone into alpha zone, same as the predicate device. |
| Stability of Anti-Daratumumab Reagent | Shelf life of 2 years at 2-8ºC. | The shelf life is 2 years at 2-8ºC, the same as the predicate. (Some studies were reported as ongoing). |
| Daratumumab Control | Must be consistent with the predicate device. | Same (K172195). |
| Concordance | 100% concordance between the predicate and modified device for sample types tested. | 100% concordance was demonstrated across all tested samples (9 negative, 21 daratumumab-treated, 21 daratumumab-spiked). |
2. Sample Size Used for the Test Set and Data Provenance
- Sample Size:
- Concordance Study: A total of 51 human serum samples were used:
- 9 negative samples (without monoclonals)
- 21 daratumumab treated patient samples
- 21 daratumumab spiked samples
- Sensitivity and Efficiency Study: 3 serum samples were used:
- 2 normal serum samples
- 1 serum with an IgG Kappa monoclonal
- Concordance Study: A total of 51 human serum samples were used:
- Data Provenance: The document does not explicitly state the country of origin or whether the data was retrospective or prospective. Given it's a 510(k) summary for a modified device, the samples were likely acquired under institutional review board (IRB) approval for research use, but specifics are not provided. The samples referred to as "human serum samples" and "daratumumab treated patient samples" suggest human origin.
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. The evaluation method described is "electrophoregrams are evaluated visually for the presence of specific reactions." This implies visual interpretation, likely by trained laboratory personnel, but no explicit details are given about expert panels.
4. Adjudication Method for the Test Set
The document does not specify any formal adjudication method (e.g., 2+1, 3+1). The evaluation is described as "visual," which suggests individual assessment, potentially followed by internal quality control.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was done
No, an MRMC comparative effectiveness study was not done. The study focused on demonstrating equivalence in performance characteristics between the modified device and its predicate, specifically around its ability to remove daratumumab interference. It did not involve comparing human reader performance with and without AI assistance.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) was done
This device is not an AI/algorithm-only device. It is an in-vitro diagnostic test kit (reagents) used in conjunction with an electrophoresis apparatus, where the final evaluation is visual and performed by a human. The "device" in this context refers to the HYDRASHIFT 2/4 daratumumab kits, which are reagents for laboratory testing.
7. The Type of Ground Truth Used
The ground truth for the performance studies appears to be based on:
- Known sample characteristics: Using "negative samples," "daratumumab-treated patient samples" (with known treatment status), and "daratumumab spiked samples" with predetermined concentrations.
- Visual evaluation of electrophoregrams: The presence or absence of specific reactions with monoclonal proteins is visually assessed, likely based on established laboratory protocols and the expected behavior of the predicate device.
It's essentially a performance comparison against known sample statuses and the established performance of the predicate device.
8. The Sample Size for the Training Set
This document does not describe a training set. This device is a reagent kit, not a machine learning or AI-based system that typically requires a training set. The performance studies are validation studies for the modified reagent.
9. How the Ground Truth for the Training Set Was Established
As there is no training set mentioned or implied for this type of device, this question is not applicable.
§ 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).