(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.
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Image /page/0/Picture/0 description: The image shows the logo for the U.S. Food and Drug Administration (FDA). The logo consists of two parts: the Department of Health & Human Services logo on the left and the FDA text logo on the right. The text logo has the letters "FDA" in a blue square, followed by the words "U.S. FOOD & DRUG ADMINISTRATION" in blue.
November 12, 2021
Sebia Karen Anderson Director of Regulatory 1705 Corporate Drive Suite 400 Norcross, Georgia 30096
Re: K203184
Trade/Device Name: HYDRASHIFT 2/4 isatuximab 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: October 15, 2020 Received: October 27, 2020
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
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statutes and regulations administered by other Federal agencies. You must comply with all the Act's 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/combination-products/guidance-regulatory-information/postmarketing-safety-reportingcombination-products); good manufacturing practice requirements as set forth in the quality systems (QS) 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 https://www.fda.gov/medical-device-safety/medical-device-reportingmdr-how-report-medical-device-problems.
For comprehensive regulatory information about medical devices and radiation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/medicaldevices/device-advice-comprehensive-regulatory-assistance) and CDRH Learn (https://www.fda.gov/training-and-continuing-education/cdrh-learn). 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 (https://www.fda.gov/medical-device-advice-comprehensive-regulatoryassistance/contact-us-division-industry-and-consumer-education-dice) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).
Sincerely,
Ying Mao, Ph.D. Chief 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) K203184
Device Name HYDRASHIFT 2/4 isatuximab
Indications for Use (Describe)
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.
| Type of Use (Select one or both, as applicable) |
|---|
| ------------------------------------------------- |
X 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 |
|---|---|
| Address | 1705 Corporate Drive Suite 400Norcross, Georgia 30093, USA |
| Contact | Karen Anderson, Dir of RegulatoryPhone: 1-800-835-6497Fax: 770-446-8511Email: karen.anderson@sebia-usa.comMatthew Wagner, Ph.D.Scientific Affairs SpecialistPhone: 1-800-835-6497Email: matthew.wagner@sebia-usa.com |
| Date Prepared | November 9, 2021 |
| Manufacturing | SebiaParc Technologique Léonard de VinciRue Léonard 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 isatuximab |
| Common Name | Hydrashift isatuximab Serum Immunofixation |
| Product Regulation No. | 21CFR sec. 866.5510 |
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| Product Codes | CFF |
|---|---|
| Device classification and PanelClassification | Class II, Immunology |
| Establishment Registration No. | 8023024 |
1. DEVICE DESCRIPTION
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.
Reagents: REAGENTS AND MATERIALS SUPPLIED IN THE HYDRASHIFT 2/4 isatuximab KIT
| ITEMS | PN 4642(40 TESTS) |
|---|---|
| Anti-isatuximab antiserum (ready touse) | 1 vial, 0.8 mL |
| Sample diluent (ready to use) | 1 vial, 2,2 mL |
| Green applicators (ready to use) | 2 packs of 10(15 teeth) |
REAGENTS REQUIRED BUT NOT SUPPLIED
| SEBIA PRODUCT NUMBER | |
|---|---|
| HYDRAGEL 2 or 4 IFAcid violet - Dynamic mask | 4302, 4304 or 4381* |
| Antisera and Fixative for immunofixation IF -Dynamic maskor | 4315 |
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| HYDRAGEL 2 or 4 IFAcid violet - Standard mask | 4802, 4804 or 4881* |
|---|---|
| Antisera and Fixative for immunofixation IFStandard mask | 4815 |
| and | |
| isatuximab CONTROL | 4764 |
| DESTAINING SOLUTION | 4540 |
| HYDRASYS WASH SOLUTION | 4541 |
| HYDRAGEL IF SAMPLE DILUENT | 4588 |
| FLUIDIL | 4587 |
| DTT DILUENT (IF / IT) | 4589 |
| BETA-MERCAPTOETHANOL (BME or2MERCAPTOETHANOL) | Not supplied by SEBIA |
2. INDICATIONS FOR USE
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 lgG kappa interference and enables the visual evaluation of the presence or absence of monoclonal proteins on HYDRAGEL IF kits in patients who have received isatuximab therapy.
For In Vitro Diagnostic use. For Prescription Use Only.
3. TECHNOLOGICAL CHARACTERISTICS
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.
4. SUBSTANTIAL EQUIVALENCE INFORMATION:
| Predicate Device Name | Predicate Device510(k) number | Product Code | Regulation No |
|---|---|---|---|
| HYDRAGEL IF | K960669 | CFF | 866.5510 |
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Similarities between the candidate device (HYDRASHIFT 2/4 isatxumiab) and the predicate device (HYDRAGEL IF) (Table A).
| Similarities | ||||||||
|---|---|---|---|---|---|---|---|---|
| Table A | HYDRASHIFT 2/4 isatuximabCandidate Device | HYDRAGEL IFPredicate DeviceK960669 | ||||||
| IntendedUse /IndicationsFor Use | The HYDRASHIFT 2/4 isatuximab kit isintended for the qualitative detection ofmonoclonal proteins in human serum byimmunofixation electrophoresis. TheHYDRASHIFT 2/4 isatuximab kit is to be usedin conjunction with the HYDRAGEL IF kit andthe semi-automated HYDRASYS 2electrophoresis apparatus. Theelectropherograms are evaluated visually forthe presence of specific reactions with thesuspect monoclonal proteins. TheHYDRASHIFT 2/4 isatuximab kit removesisatuximab IgG kappa interference andenables the visual evaluation of the presenceor absence of monoclonal proteins onHYDRAGEL IF kits in patients who havereceived isatuximab therapy.For In Vitro Diagnostic use. For PrescriptionUse Only. | The HYDRAGEL 1 IF, 2 IF, 4 IFand 9 IF kits are designed fordetection of monoclonal proteinsin human serum and urine byimmunofixation electrophoresis.The kits are used in conjunctionwith the semi-automatedHYDRASYS electrophoresisapparatus. The proteins,separated by electrophoresis onalkaline buffered agarose gels, areincubated with individual antiserathat are specific against gamma(Ig G), alpha (Ig A) and mu (Ig M)heavy chains, and kappa (free andbound) and lambda (free andbound) light chains, respectively.After removing the non-reactedproteins, the immunoprecipitatesare stained either with acid violetor amidoblack. Theelectrophoregrams are evaluatedvisually for the presence ofspecific reactions with the suspectmonoclonal proteins. | ||||||
| AssayPrinciple | Agarose Gel Electrophoresis | Agarose Gel Electrophoresis | ||||||
| SoftwareProgram | Same | IF Program |
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Table B. Differences between the predicate device (HYDRAGEL IF) and the candidate device (HYDRASHIFT 2/4 isatuximab) in (Table B).
| Differences | |||||||
|---|---|---|---|---|---|---|---|
| Table B | HYDRASHIFT 2/4 isatuximabCandidate Device | HYDRAGEL IFPredicate Device K960669 | |||||
| Specimen Type | Human Serum | Human Serum, Human Urine | |||||
| Reagents | Using anti-isatuximab antibody | No anti-isatuximab antibody | |||||
| isatuximabband | Removed from gamma zone intoalpha zone | Remains in Gamma zone |
5. Performance Data:
a) Repeatability
Ten (10) different samples, including two (2) samples without the addition of isatuximab (isatuximab CONTROL and Normal Control Serum) and 8 samples with addition of isatuximab (samples 3 to 10 with monoclonal component).
Samples 3 to 10 were also analyzed native to verify the concordance between native and spiked samples were run using the HYDRASHIFT 2/4 isatuximiab procedure used in conjunction with each of the following kits- HYDRAGEL 4 IF Acid violet Standard mask and HYDRAGEL 4 IF Acid Violet Dyamic mask.
Each sample was run 4 times within the same gel.
For each tested sample, all repeats gave 100% concordant results within the gel.
| Sample No. | Type | Within gel | Total analyses per gel |
|---|---|---|---|
| Sample No. 1 | Isatuximab Control | 100% concordant result | 4 |
| Sample No. 2 | Normal Control | 100% concordant result | 4 |
| Sample No. 3 | IgG kappa | 100% concordant result | 4 |
| Sample No. 4 | IgG lambda | 100% concordant result | 4 |
| Sample No. 5 | IgA kappa | 100% concordant result | 4 |
| Sample No. 6 | IgA lambda | 100% concordant result | 4 |
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| Sample No. 7 | IgM kappa | 100% concordantresult | 4 |
|---|---|---|---|
| Sample No. 8 | IgM lambda +IgA kappa | 100% concordantresult | 4 |
| Sample No. 9 | Kappa Free | 100% concordantresult | 4 |
| Sample No. 10 | Lambda free | 100% concordantresult | 4 |
b) Reproducibility between gels, between lots and between instruments
Eight (8) different serum samples with monoclonal components were run using the HYDRASHIFT 2/4 isatuximab procedure used in conjunction with HYDRAGEL 4 IF Acid violet Standard mask and the HYDRAGEL 4 IF Acid violet Dynamic mask
A Normal Control Serum was analyzed on 9 runs with one analysis per gel, over 3 working days, it gave 100 % of concordant results between gels on the 3 HYDRASYS 2 instruments and with 3 lots of HYDRASHIFT 2/4 isatuximab kit over 3 working days
This study was performed with 3 HYDRASYS 2 instruments and with 3 lots of HYDRASHIFT 2/4 isatuximab kit over 3 working days.
Each sample was analyzed on 9 runs with one analysis per gel, over 3 working days. All samples gave 100% concordant results between gels on the 3 HYDRASYS 2 instruments.
| SampleNo. | Type | Instrument No. 1/Kit lot No. 1 | Instrument No. 2/Kit lot No. 2 | Instrument No. 3/Kit lot No. 3 | Totalanalyses persample | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Day No. 1 | Day No. 2 | Day No. 3 | Day No. 1 | Day No. 2 | Day No. 3 | Day No. 1 | Day No. 2 | Day No. 3 | |||
| 2 | Normal | 100 %concordantresult | 100 %concordantresult | 100 %concordantresult | 100 %concordantresult | 100 %concordantresult | 100 %concordantresult | 100 %concordantresult | 100 %concordantresult | 100 %concordantresult | 9 |
| 3 | IgGkappa | 100 %concordantresult | 100 %concordantresult | 100 %concordantresult | 100 %concordantresult | 100 %concordantresult | 100 %concordantresult | 100 %concordantresult | 100 %concordantresult | 100 %concordantresult | 9 |
| 4 | IgGlambda | 100 %concordantresult | 100 %concordantresult | 100 %concordantresult | 100 %concordantresult | 100 %concordantresult | 100 %concordantresult | 100 %concordantresult | 100 %concordantresult | 100 %concordantresult | 9 |
| 5 | IgAkappa | 100 %concordantresult | 100 %concordantresult | 100 %concordantresult | 100 %concordantresult | 100 %concordantresult | 100 %concordantresult | 100 %concordantresult | 100 %concordantresult | 100 %concordantresult | 9 |
| 6 | IgAlambda | 100 %concordantresult | 100 %concordantresult | 100 %concordantresult | 100 %concordantresult | 100 %concordantresult | 100 %concordantresult | 100 %concordantresult | 100 %concordantresult | 100 %concordantresult | 9 |
| 7 | IgMkappa | 100 %concordantresult | 100 %concordantresult | 100 %concordantresult | 100 %concordantresult | 100 %concordantresult | 100 %concordantresult | 100 %concordantresult | 100 %concordantresult | 100 %concordantresult | 9 |
| 8 | IgMlambda +IgAkappa | 100 %concordantresult | 100 %concordantresult | 100 %concordantresult | 100 %concordantresult | 100 %concordantresult | 100 %concordantresult | 100 %concordantresult | 100 %concordantresult | 100 %concordantresult | 9 |
| 9 | Kappafree | 100 %concordantresult | 100 %concordantresult | 100 %concordantresult | 100 %concordantresult | 100 %concordantresult | 100 %concordantresult | 100 %concordantresult | 100 %concordantresult | 100 %concordantresult | 9 |
| 10 | Lambdafree | 100 %concordantresult | 100 %concordantresult | 100 %concordantresult | 100 %concordantresult | 100 %concordantresult | 100 %concordantresult | 100 %concordantresult | 100 %concordantresult | 100 %concordantresult | 9 |
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The isatuximab CONTROL was analyzed on 9 runs including one analysis per gel on 3 gels over 3 working days.
The isatuximab CONTROL gave 100% concordant results between gels on the 3 HYDRASYS 2 instruments and with 3 lots of HYDRASHIFT 2/4 isatuximab kit over 3 working days.
| SampleNo. | Type | Instrument No. 1 /Kit No. 1 | Instrument No. 2 /Kit No. 2 | Instrument No. 3 /Kit No. 3 | Totalanalysespersample | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Day No. 1 | Day No. 2 | Day No. 3 | Day No. 1 | Day No. 2 | Day No. 3 | Day No. 1 | Day No. 2 | Day No. 3 | |||
| 1 | Normal | 100 %concordantresult | 100 %concordantresult | 100 %concordantresult | 100 %concordantresult | 100 %concordantresult | 100 %concordantresult | 100 %concordantresult | 100 %concordantresult | 100 %concordantresult | 27 |
c) Comparative studies
The results presented below have been obtained from 1 internal study and 2 external studies performed in the USA. The external study No. 1 was performed on 204 samples and the external study No. 2 was performed on 203 samples. The same serum samples were analyzed in both external studies with exception of one sample included in external study 1.
Internal study
The internal study was conducted on 53 serum samples analyzed with HYDRASHIFT 2/4 isatuximab procedure used in conjunction with each of the following kits :
-
HYDRAGEL 4 IF Acid violet Standard mask,
-
HYDRAGEL 4 IF Acid violet Dynamic mask,
-
HYDRAGEL 2 IF Acid violet Standard mask,
-
HYDRAGEL 2 IF Acid violet Dynamic mask.
This study, conducted between native samples and the same samples added with isatuximab (spiked samples), demonstrated a 100% complete agreement:
-
For 26 normal serum samples: 100% concordant results.
-
For 27 pathological serum samples: 100% concordant results.
In both types of samples, monoclonal proteins were detected and characterized with 100 % of concordance.
| Characterization | Number of serumsamples |
|---|---|
| Normal | 26 |
| IgG kappa | 9 |
| IgG lambda | 4 |
| IgA kappa | 3 |
| IgA lambda | 3 |
| IgM kappa | 3 |
| IgM lambda | 2 |
| Kappa free | 3 |
| Total | 53 |
510(k) Summary 7
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External study No. 1
Comparative study No. 1 was performed on 204 serum samples analyzed with:
-
HYDRAGEL 4 IF Acid Violet Dynamic Mask kit,
-
HYDRASHIFT 2/4 isatuximab used in coniunction with HYDRAGEL 4 IF Acid Violet Dynamic Mask kit.
With the HYDRAGEL 4 IF Acid Violet Dynamic Mask procedure, the isatuximab was visualized on G track and on Kappa track for 90 samples. For those samples, the HYDRASHIFT 2/4 isatuximab used in conjunction with HYDRAGEL 4 IF Acid Violet Dynamic Mask kit allows the shifting of the isatuximab.
For the other 114 samples, the characterization (normal or abnormal with monoclonal components) was the same between both procedures.
This study demonstrated 100% concordant result:
-
For 69 normal serum samples: 100% concordant result.
-
For the 135 pathological serum samples: 100% concordant result.
| 2 IgA kappa | 1 |
|---|---|
| 2 IgG kappa | 2 |
| 2 IgM kappa + IgG lambda | 1 |
| 2 Lambda | 1 |
| IgA kappa | 17 |
| IgA kappa + IgG kappa | 1 |
| IgA lambda | 10 |
| IgA lambda + IgG lambda | 1 |
| IgA lambda + Lambda | 4 |
| IgG kappa | 45 |
| IgG kappa + IgG lambda | 5 |
| IgG kappa + Kappa | 1 |
| IgG kappa + Lambda | 2 |
| IgG lambda | 29 |
| IgG lambda + Lambda | 5 |
| Kappa | 2 |
| Lambda | 8 |
| Normal | 69 |
| Total | 204 |
External study No. 2
Comparative study No. 2 was performed on 203 serum samples analyzed with:
-
HYDRAGEL 4 IF Acid Violet Standard Mask kit,
-
HYDRASHIFT 2/4 isatuximab used in conjunction with HYDRAGEL 4 IF Acid Violet Standard Mask kit. With the HYDRAGEL 4 IF Acid Violet Standard Mask procedure, the isatuximab was visualized on G track and on Kappa track for 90 samples. For those samples, the HYDRASHIFT 2/4 isatuximab used in coniunction with HYDRAGEL 4 IF Acid Violet Standard Mask kit allows the shifting of the isatuximab.
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For the other 113 samples, the characterization (normal or abnormal with monoclonal components) was the same between both procedures.
This study demonstrated 100 % concordant result:
-
For 68 normal serum samples: 100 % concordant result.
-
For the 135 pathological serum samples: 100 % concordant result.
| 2 IgA kappa | 1 |
|---|---|
| 2 IgG kappa | 2 |
| 2 IgM kappa + IgGlambda | 1 |
| 2 Lambda | 1 |
| IgA kappa | 17 |
| IgA kappa + IgG kappa | 1 |
| IgA lambda | 10 |
| IgA lambda + IgGlambda | 1 |
| IgA lambda + Lambda | 4 |
| IgG kappa | 45 |
| IgG kappa + IgG lambda | 5 |
| IgG kappa + Kappa | 1 |
| IgG kappa + Lambda | 2 |
| IgG lambda | 29 |
| IgG lambda + Lambda | 5 |
| Kappa | 2 |
| Lambda | 8 |
| Normal | 68 |
| Total | 203 |
d) Sensitivity
Five (5) serum samples, added with isatuximab at different concentrations (final concentrations in sample between 0.1 and 3.0 g/L), were analyzed with the HYDRASHIFT 2/4 isatuximab procedure used in conjunction with each of the following kits:
-
HYDRAGEL 4 IF Acid Violet Standard Mask,
-
HYDRAGEL 4 IF Acid Violet Dynamic Mask.
The detection limit of isatuximab and / or isatuximab / anti-isatuximab antibody complex visualized is 0.3 g/L.
e) Controls
It is recommended to run assay control serum (such as isatuximab CONTROL, SEBIA PN 4764) after each reagent lot change.
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f) Interferences
The common interfering factors with the HYDRASHIFT 2/4 isatuximab procedure (bilirubin, triqlycerides, hemoglobin and rheumatoid factor) were evaluated in studies based on the Clinical Laboratory Standards Institute (CLSI-USA) EP07, 3rd ed guideline "Interference Testing in Clinical Chemistry; Third Edition". HAMA (Human Anti-Mouse Antibody) interference testing was also included in the interference study.
Additional inferference studies included: Pomalidomide, Carfilzomib, Dexamethasone, Ixazomib, Cyclophosphamide, Melphalan, Prednisone, Lenalidomide Bortezomib,). The results are summarized below
No interference with the HYDRASHIFT 2/4 isatuximab procedure was detected due to the serum sample's concentration of the following interfering factors tested at levels equal to the concentrations listed below:
| Endogenous Interfering factor | Concentration |
|---|---|
| Unconjugated bilirubin | 20 mg/dL (342 $\mu$ M) |
| Conjugated bilirubin | 20 mg/dL (342 $\mu$ M) |
| Triglycerides | 3.00 g/dL (33.96 mM) |
| Hemoglobin | 0.2 g/dL |
| Rheumatoid factor | 2000 IU/mL |
| Human Anti-Mouse Antibody (HAMA) | Titer: 640 |
Drug Interference
No interference with the HYDRASHIFT 2/4 isatuximab procedure was detected due to the serum sample's high concentration of the following interfering factors tested at levels equal to the concentrations listed below:
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| Interfering factor | Concentration |
|---|---|
| Pomalidomide | 1 mg/L |
| Carfilzomib | 1 mg/L |
| Dexamethasone | 1 mg/L |
| Ixazomib | 1 mg/L |
| Cyclophosphamide | 1 mg/L |
| Melphalan | 1 mg/L |
| Prednisone | 1 mg/L |
| Lenalidomide | 4 mg/L |
| Bortezomib | 2 mg/L |
6. International Myeloma Working Group (IMWG) Response Criteria
As discussed in the current International Myeloma Working Group response criteria guidelines1 serum protein electrophoresis (SPEP) and Immunofixation (IF) are part of the current IMWG standard of practice recommendations for monitoring responses and relapses in multiple myeloma. International quidelines such as the National Comprehensive Cancer Network Clinical Practice Guidelines for Multiple Myeloma (NCCN) use reductions of monoclonal protein by SPEP and normalization of IFE to stratify response.
- Kumar S, Paiva B, Anderson KC, Durie B, Landgren O, Moreau P, Munshi N, Lonial S, Bladé J. Mateos MV. Dimopoulos M. Kastritis E. Boccadoro M. Orlowski R. Goldschmidt H, Spencer A, Hou J, Chng WJ, Usmani SZ, Zamagni E, Shimizu K, Jagannath S, Johnsen HE, Terpos E, Reiman A, Kyle RA, Sonneveld P, Richardson PG, McCarthy P, Ludwig H, Chen W, Cavo M, Harousseau JL, Lentzsch S, Hillengass J, Palumbo A, Orfao A, Rajkumar SV, Miguel JS, Avet-Loiseau H. International Myeloma Working Group consensus criteria for response and minimal residual disease assessment in multiple myeloma. The Lancet Oncol. 2016 Aug;17(8):e328-e346. doi: 10.1016/S1470-2045(16)30206-6. PMID: 27511158.
7. Conclusion:
The submitted information in this premarket notification is complete and supports a substantial equivalence decision.
§ 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).