(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.
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May 2, 2019
Sebia Karen Anderson Director of Regulatory and Technical 1705 Corporate Drive, Suite 400 Norcross, Georgia 30093
Re: K190851
Trade/Device Name: HYDRASHIFT 2/4 daratumumab Regulation Number: 21 CFR 866.5510 Regulation Name: Immunoglobulins A. G. M. D. and E immunological test system Regulatory Class: Class II Product Code: CFF Dated: March 5, 2019 Received: April 2, 2019
Dear Karen Anderson:
We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food, Drug, and Cosmetic Act (Act) that do not require approval of a premarket approval application (PMA). You may, therefore, market the device, subject to the general controls provisions of the Act. Although this letter refers to your product as a device, please be aware that some cleared products may instead be combination products. The 510(k) Premarket Notification Database located at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/pmn.cfm identifies combination product submissions. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you; however, that device labeling must be truthful and not misleading.
If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. In addition, FDA may publish further announcements concerning your device in the Federal Register.
Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's
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requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Part 801 and Part 809); medical device reporting of medical device-related adverse events) (21 CFR 803) for devices or postmarketing safety reporting (21 CFR 4, Subpart B) for combination products (see https://www.fda.gov/CombinationProducts/GuidanceRegulatoryInformation/ucm597488.htm); good manufacturing practice requirements as set forth in the quality systems (OS) regulation (21 CFR Part 820) for devices or current good manufacturing practices (21 CFR 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.
Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm.
For comprehensive regulatory information about mediation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/) and CDRH Learn (http://www.fda.gov/Training/CDRHLearn). Additionally, you may contact the Division of Industry and Consumer Education (DICE) to ask a question about a specific regulatory topic. See the DICE website (http://www.fda.gov/DICE) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).
Sincerely,
Doug Jeffery Acting Deputy Director Division of Immunology and Hematology Devices OHT7: Office of In Vitro Diagnostics and Radiological Health Office of Product Evaluation and Quality Center for Devices and Radiological Health
Enclosure
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Indications for Use
510(k) Number (if known) K190851
Device Name HYDRASHIFT 2/4 daratumumab
Indications for Use (Describe)
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.
Type of Use (Select one or both, as applicable)
| Prescription Use (Part 21 CFR 801 Subpart D) | |
|---|---|
| Over-The-Counter Use (21 CFR 801 Subpart C) |
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510K SUMMARY (Summary of Safety and Effectiveness)
This summary of 510(k) safety and effectiveness information is being submitted in accordance with the requirements of 21 CFR 807.92.
| Submitter Name | Sebia, Inc. |
|---|---|
| Address | 1705 Corporate Drive Suite 400Norcross, Georgia 30093, USA |
| Contact | Karen Anderson, Dir of Technical and RegulatoryPhone: 1-800-835-6497Fax: 770-446-8511Email: karen.anderson@sebia-usa.comMatthew C. Wagner, Ph.DScientific Affairs SpecialistPhone: 1-800-835-6497Email: matthew.wagner@sebia-usa.com |
| Date Prepared | March 5, 2019 |
| Manufacturing | SebiaParc Technologique L\u00e9onard de VinciRue L\u00e9onard de Vinci,CP 8010 LISSES, 91008 EVRY CedexFRANCEPhone: (33) 1 69 89 80 80Fax: (33) 1 69 89 78 78 |
| Product Name | HYDRASHIFT 2/4 daratumumab |
| Common Name | Hydrashift daratumumab Serum Immunofixation |
| Product Regulation No. | 21CFR sec. 866.5510 |
| Product Codes | CFF |
| Device classification and PanelClassification | Class II , Immunology (82) |
| Establishment Registration No. | 8023024 |
| Predicate Devices | The candidate device is a modification of thepredicate device. The device name , HYDRASHIFT2/4 daratumumab, is unchanged from how it wascleared in 510(k) K172195 |
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1. DEVICE DESCRIPTION
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.
2. INDICATIONS FOR USE
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.
510(k) Summary 2
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For In Vitro Diagnostic Prescription Use Only.
Note: The intended use of the modified device, as described in its labeling, has not changed as the result of the modification.
3. TECHNOLOGICAL CHARACTERISTICS
The candidate device, HYDRASHIFT 2/4 daratumumab, has been modified from the predicate device with the addition to the package insert labeling as follows:
- Additional to the Anti daratumumab reagent provided in the kit, . The anti-daratumumab antiserum is ready to use. It contains anti-daratumumab total immunoglobulins from Chinese hamster ovary cells (CHO). For easy identification of the antiserum and as an aid in monitoring its application, the antiserum is colored with distinct nonhazardous dye that matches the color of the vial label.
The following tables compare the HYDRASHIFT 2/4 daratumumab with its predicate device, HYDRASHIFT 2/4 daratumumab (K172195)
| Table 1: Assay ComparisonItem | HYDRASHIFT 2/4 daratumumabPredicate Device (K172195) | HYDRASHIFT 2/4 daratumumabCandidate/ModifiedDevice |
|---|---|---|
| Intended Use | 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 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. For In Vitro Diagnostic Prescription Use Only. | Same |
| Instrumentation | Sebia HYDRASYS 2 | Same |
Table 1: Assav Comparison
510(k) Summary 3
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| Immunofixation (IF) test kits usedin conjuction withthe HYDRASHIFT2/4 daratumumab | HYDRAGEL 4 IF Acid violetStandard mask,HYDRAGEL 4 IF Acid violetDynamic mask. | Same |
|---|---|---|
| ScientificTechnology | Agarose Gel Electrophoresis | Same |
| Specimen Type | Serum | Same |
| Results | Qualitative | Same |
| Sensitivity/ Lowest detectabledaratumumab limit | The detection limit of daratumumaband / or daratumumab / anti-daratumumab antibodycomplexvisualized is 0.3 g/L | Same |
| Efficiency ( Maximum removal ofcomplex) | 3.0 g/L | Same |
| DaratumumabbandwhenHYDRASHIFTtreatedwithdaratumumab kit | Removed from gamma zone intoalpha zone | Same |
| Stability of the anti-daratumumabreagentStability 2 to 8ºC | 2 years | Same |
| daratumumab Control | daratumumab control (K172195) | Same |
Table 2: Assay Comparison, Labelled Performance Characteristics
| Item | HYDRASHIFT 2/4 daratumumabPredicate Device (K172195) | HYDRASHIFT 2/4 daratumumabCandidate/Modified Device |
|---|---|---|
| Package InsertLabeling | The anti-daratumumabantiserum is ready to use.It contains murine anti-daratumumab totalimmunoglobulins.For easy identification of theantiserum and as an aid inmonitoring its application, theantiserum is colored with distinctnonhazardous dye that matchesthe color of the vial label. | The anti-daratumumab antiserum isready to use. It contains anti-daratumumab total immunoglobulinsfrom Chinese hamster ovary cells. Foreasy identification of the antiserum andas an aid in monitoring its application, theantiserum is colored with distinctnonhazardous dye that matches the colorof the vial label |
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Table 3: Kit and Components
| HYDRASHIFT 2/4 daratumumab (K172195) | HYDRASHIFT 2/4 daratumumab | ||||
|---|---|---|---|---|---|
| Items | PN 4639 (20 TESTS) | PN 4640 (40 TESTS) | Items | PN 4639 (20 TESTS) | PN 4640 (40 TESTS) |
| Anti- daratumumab mouse antiserum ( ready to use) | 1 vial, 0.4 mL | 1 vial, 0.85mL | Anti- daratumumab Chinese hamster ovary cells antiserum ( ready to use) | 1 vial, 0.4 mL | 1 vial, 0.85 mL |
| Sample diluent (ready to use) | 1 vial, 2.2 mL | 1 vial, 2.2 mL | Sample diluent (ready to use) | Same | Same |
| Green applicators | 1 pack of 10 | 2 pack of 10 | Green applicators | Same | Same |
4. Performance Data:
To address the modifications the following studies were conducted to validated the performance of the modified anti-daratumumab (CHO).
4.1 Concordance
Human serum samples of (9 negative samples without monoclonals), (21 daratumumab treated patient samples), (21 daratumumab spiked samples) were compared between the predicate ( anti-daratumumab murine) and modified device ( anti-daratumumab chinesse hamster ovary cells).
The samples demonstrated 100% concordance.
4.2 Sensitivity and Efficiency
Three serum samples (2 normal serum samples and 1 serum with a IgG Kappa monoclonal) were used in the study. Samples were mixed by adding different concentrations of daratumumab over a concentration range of 0.1 to 3.0 g/L. The detection limit (sensitivity) of the daratumumab complex at the alpha-1 zone of the G kappa tracks was visualized at 0.3 g/L the same as the predicate device. The efficiency of the shift of the daratumumab complex to the alpha-1 zone is 3.0 g/L the same as the predicate.
4.3 Stability of the anti-daratumumab
The stability of the anti-daratumumab (CHO) was tested at 2-8ºC in real time and accelerated studies using two lots of anti-daratumumab. Some studies are still on going. The shelf life is 2 years at 2-8ºC the same as the predicate.
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5. Conclusion:
The submitted information in this premarket notification is complete and supports a substantial equivalence decision. The differences between the predicate and candidate device do not impact the indications for use or technical performance of the assay.
§ 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).