(174 days)
Not Found
No
The device description and performance studies focus on a chemical and electrophoretic process with visual evaluation, and there is no mention of AI or ML in the document.
No
The device is an in vitro diagnostic (IVD) device used for detecting monoclonal proteins in human serum by immunofixation electrophoresis, which is a diagnostic function, not a therapeutic one.
Yes
The "Intended Use / Indications for Use" section explicitly states that the device is "intended for the qualitative detection of monoclonal proteins in human serum by immunofixation electrophoresis," which is a diagnostic purpose. It also states "For In Vitro Diagnostic Prescription Use Only."
No
The device description clearly states it is a "semi-automated multi-parameter system for start-to finish agarose gel electrophoresis" and mentions physical components like gels, antisera, and staining. It is a hardware system with associated reagents, not a software-only device.
Yes, this device is an IVD (In Vitro Diagnostic).
Here's why:
- Explicit Statement: The Intended Use section clearly states: "For In Vitro Diagnostic Prescription Use Only." This is the most direct indicator.
- Intended Use: The device is intended for the qualitative detection of monoclonal proteins in human serum. This involves testing a sample taken from the human body to provide information about a medical condition (the presence of monoclonal proteins, which can indicate monoclonal gammopathies).
- Device Description: The description details a laboratory procedure involving the analysis of human serum using electrophoresis and immunofixation.
- Performance Studies: The document includes performance studies (Repeatability, Reproducibility, External comparative studies, Sensitivity) which are typical for IVD devices to demonstrate their analytical performance.
- Predicate Device: A predicate device (K960669; HYDRAGEL IF) is listed, which is a common requirement for demonstrating substantial equivalence for IVD devices seeking regulatory clearance.
- Intended User/Care Setting: The intended user is a laboratory setting, which is where IVD tests are typically performed.
All these factors strongly indicate that this device is an In Vitro Diagnostic.
N/A
Intended Use / Indications for Use
Tray: 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.
Control: 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.
Product codes (comma separated list FDA assigned to the subject device)
CFF, JJY
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 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.
Reagents: REAGENTS AND MATERIALS SUPPLIED IN THE HYDRASHIFT 2/4 daratumumab KITS
| ITEMS | PN 4639 (20 TESTS) | PN 4640 (40 TESTS) |
|---|---|---|
| Anti-daratumumab 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 |
| Green applicators (ready to use) | 1 pack of 10 (15 teeth) | 2 packs of 10 (15 teeth) |
REAGENTS REQUIRED BUT NOT SUPPLIED
| SEBIA PRODUCT NUMBER | |
|---|---|
| HYDRAGEL 2 or 4 IF | |
| Acid violet - Dynamic mask | 4302, 4304 or 4381* |
| Antisera and Fixative for immunofixation IF - | |
| Dynamic mask | |
| or | 4315 |
| HYDRAGEL 2 or 4 IF | |
| Acid violet - Standard mask | 4802, 4804 or 4881* |
| Antisera and Fixative for immunofixation IF - | |
| Standard mask | |
| and | 4815 |
| Daratumumab CONTROL | 4765 |
| DESTAINING SOLUTION | 4540 |
| HYDRASYS WASH SOLUTION | 4541 |
| HYDRAGEL IF SAMPLE DILUENT | 4588 |
| FLUIDIL | 4587 |
| DTT DILUENT (IF / IT) | 4589 |
| BETA-MERCAPTOETHANOL (BME or | |
| 2MERCAPTOETHANOL) | Not supplied by SEBIA |
Mentions image processing
Not Found
Mentions AI, DNN, or ML
Not Found
Input Imaging Modality
Not Found
Anatomical Site
Not Found
Indicated Patient Age Range
Not Found
Intended User / Care Setting
Laboratory use.
Description of the training set, sample size, data source, and annotation protocol
Not Found
Description of the test set, sample size, data source, and annotation protocol
Not Found
Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)
a) Repeatability:
Ten (10) different serum samples, including 1 normal serum sample and 9 serum samples with monoclonal components, were run using the HYDRASHIFT 2/4 daratumumab procedure used in conjunction with each of the following kits: - HYDRAGEL 4 IF Acid violet Standard mask, -HYDRAGEL 4 IF Acid violet Dynamic mask.
Each sample was run 4 times within the same gel.
For each tested sample, all repeats gave 100 % of concordant results within gel.
b) Reproducibility between gels, between lots and between instruments:
Ten (10) different serum samples, including 1 normal serum sample and 9 serum samples with monoclonal components, were run using the HYDRASHIFT 2/4 daratumumab procedure used in conjunction with each of the following kits : - HYDRAGEL 4 IF Acid violet Standard mask, - HYDRAGEL 4 IF Acid violet Dynamic mask.
This study was performed with 3 HYDRASYS 2 instruments and with 3 lots of HYDRASHIFT 2/4 daratumumab kit.
The normal sample was analyzed on 9 runs including one analysis per qel on 3 gels over 3 working days.
The samples with monoclonal components were analyzed on 9 runs with one analysis per gel, over 3 working days.
All samples gave 100 % of concordant results between gels on the 3 HYDRASYS 2 instruments and with 3 lots of HYDRASHIFT 2/4 daratumumab kit.
c) External comparative studies:
Study No. 1: 198 serum samples.
Study No. 2: 172 serum samples.
External study No. 1: Comparative study No. 1 was performed on 198 serum samples analyzed with: - HYDRAGEL 4 IF Acid Violet Dynamic Mask kit, - HYDRASHIFT 2/4 daratumumab used in conjunction with HYDRAGEL 4 IF Acid Violet Dvnamic Mask kit.
With the HYDRAGEL 4 IF Acid Violet Dynamic Mask procedure, the daratumumab was visualized on G track and on Kappa track for 113 samples. For those samples, the HYDRASHIFT 2/4 daratumumab used in conjunction with HYDRAGEL 4 IF Acid Violet Dynamic Mask kit allows the shifting of the daratumumab.
For the other 85 samples, the characterization (normal or abnormal with monoclonal components) was the same between both procedures.
This study demonstrated 100 % concordant result: - For 42 normal serum samples: 100 % concordant result. - For the 156 pathological serum samples: 100 % concordant result.
External study No. 2: Comparative study No. 2 was performed on 172 serum samples analyzed with: - HYDRAGEL 4 IF Acid Violet Standard Mask kit, . - HYDRASHIFT 2/4 daratumumab used in conjunction with HYDRAGEL 4 IF Acid Violet - Standard Mask kit.
With the HYDRAGEL 4 IF Acid Violet Standard Mask procedure, the daratumumab was visualized on G track and on Kappa track for 98 samples, the HYDRASHIFT 2/4 daratumumab used in conjunction with HYDRAGEL 4 IF Acid Violet Standard Mask kit allows the shifting of the daratumumab.
For the other 74 samples, the characterization (normal or abnormal with monoclonal components) was the same between both procedures.
This study demonstrated 100 % concordant result: - For 38 normal serum samples: 100 % concordant result. - For the 134 pathological serum samples: 100 % concordant result.
d) Sensitivity:
Six (6) serum samples, including 2 normal serum samples and 4 serum samples with different monoclonal components, added with daratumumab at different concentrations (final concentrations in sample between 0.1 and 3.0 g/L) were analyzed with the HYDRASHIFT 2/4 daratumumab 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 daratumumab /anti-daratumumab /anti-daratumumab antibody complex visualized is 0.3 q/L.
e) Controls:
It is recommended to run an assayed control serum (such as daratumumab CONTROL, SEBIA PN 4765) after each change of lot of a reagent.
f) Interferences:
Common interfering factors (bilirubin, triglycerides, hemoglobin and rheumatoid factor) and additional interferences (Human Anti-Mouse Antibody (HAMA, Pomalidomide, Lenalidomide, Dexamethasone, Bortezomib) were evaluated.
No interference with the HYDRASHIFT 2/4 daratumumab procedure was detected due to the serum sample's concentration of the following interfering factors tested at levels equal to the concentrations listed.
Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)
Repeatability: 100% concordant results within gel.
Reproducibility: 100% concordant results between gels on the 3 HYDRASYS 2 instruments and with 3 lots of HYDRASHIFT 2/4 daratumumab kit.
External comparative studies: 100% concordant results for both normal and pathological serum samples.
Sensitivity: The detection limit of daratumumab /anti-daratumumab /anti-daratumumab antibody complex visualized is 0.3 q/L.
Predicate Device(s): If the device was cleared using the 510(k) pathway, identify the Predicate Device(s) K/DEN number used to claim substantial equivalence and list them here in a comma separated list exactly as they appear in the text. List the primary predicate first in the list.
Reference Device(s): Identify the Reference Device(s) K/DEN number and list them here in a comma separated list exactly as they appear in the text.
Not Found
Predetermined Change Control Plan (PCCP) - All Relevant Information for the subject device only (e.g. presence / absence, what scope was granted / cleared under the PCCP, any restrictions, etc).
Not Found
§ 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).
0
Image /page/0/Picture/0 description: The image shows the logo of the U.S. Food and Drug Administration (FDA). On the left is the Department of Health & Human Services logo. To the right of that is the FDA logo, which is a blue square with the letters "FDA" in white. To the right of the blue square is the text "U.S. FOOD & DRUG ADMINISTRATION" in blue.
January 11, 2018 Sebia, Inc Karen Anderson Director of Technical and Regulatory 1705 Corporate Drive, Suite 400 Norcross, Georgia 30093
Re: K172195
Trade/Device Name: HYDRASHIFT 2/4 daratumumab, daratumumab Control Regulation Number: 21 CFR 866.5510 Regulation Name: Immunoglobulins A, G, M, D, and E immunological test system Regulatory Class: Class II Product Codes: CFF. JJY Dated: December 07, 2017 Received: December 12, 2017
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. 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 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); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR
1
Part 820); 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 the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance.
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. Kelly Oliner -S
For, Lea Carrington Director Division of Immunology and Hematology Devices Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health
Enclosure
2
Indications for Use
510(k) Number (if known) K172195
Device Name HYDRASHIFT 2/4 daratumumab Daratbumumab Control
Indications for Use (Describe)
Assay:
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.
Control:
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.
| 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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3
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 400 |
| Norcross, Georgia 30093, USA | |
| Contact | Karen Anderson, Dir of Technical and Regulatory |
| Phone: 1-800-835-6497 | |
| Fax: 770-446-8511 | |
| Email: karen.anderson@sebia-usa.com |
Youssef Maakaroun, MD, Medical Affairs Director
Phone 1-800-835-6497
Fax 770-446-8511
Email: youssef.maakaroun@sebia-usa.com |
| Date Prepared | January 4, 2018 |
| Manufacturing | Sebia
Parc Technologique L\u00e9onard de Vinci
Rue L\u00e9onard de Vinci,
CP 8010 LISSES, 91008 EVRY Cedex
FRANCE
Phone: (33) 1 69 89 80 80
Fax: (33) 1 69 89 78 78 |
| Product Name | HYDRASHIFT 2/4 daratumumab
Daratumumab CONTROL |
| Common Name | Hydrashift daratumumab Serum Immunofixation |
| Product Regulation No. | 21CFR sec. 866.5510 |
| Product Codes | CFF |
| Device classification and Panel
Classification | Class II , Immunology |
| Establishment Registration No. | 8023024 |
4
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 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.
Reagents: REAGENTS AND MATERIALS SUPPLIED IN THE HYDRASHIFT 2/4 daratumumab KITS
| ITEMS | PN 4639 (20 TESTS) | PN 4640 (40 TESTS) |
|---|---|---|
| Anti-daratumumab 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 |
| Green applicators (ready to use) | 1 pack of 10 (15 teeth) | 2 packs of 10 (15 teeth) |
REAGENTS REQUIRED BUT NOT SUPPLIED
| SEBIA PRODUCT NUMBER | |
|---|---|
| HYDRAGEL 2 or 4 IF | |
| Acid violet - Dynamic mask | 4302, 4304 or 4381* |
| Antisera and Fixative for immunofixation IF - | |
| Dynamic mask | |
| or | 4315 |
| HYDRAGEL 2 or 4 IF | |
| Acid violet - Standard mask | 4802, 4804 or 4881* |
| Antisera and Fixative for immunofixation IF - | |
| Standard mask | |
| and | 4815 |
| Daratumumab CONTROL | 4765 |
| DESTAINING SOLUTION | 4540 |
| HYDRASYS WASH SOLUTION | 4541 |
5
| HYDRAGEL IF SAMPLE DILUENT | 4588 |
|---|---|
| FLUIDIL | 4587 |
| DTT DILUENT (IF / IT) | 4589 |
| BETA-MERCAPTOETHANOL (BME or | |
| 2MERCAPTOETHANOL) | Not supplied by SEBIA |
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 by electrophoresis on alkaline buffered agarose gels, are incubated with individual antisera that are specific against gamma (lg G), alpha (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 Iq 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 the 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 sample. For In Vitro Diagnostic Prescription Use Only.
3. TECHNOLOGICAL CHARACTERISTICS
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.
4. SUBSTANTIAL EQUIVALENCE INFORMATION:
| Predicate Device Name | Predicate Device
510(k) number | Product Code | Regulation
No. |
|-----------------------|-----------------------------------|--------------|-------------------|
| HYDRAGEL IF | K960669 | CFF | 866.5510 |
6
Similarities between the candidate device (HYDRASHIFT 2/4 daratumumab) and the predicate device (HYDRAGEL IF) (Table A).
| Similarities | ||
|---|---|---|
| Table A | HYDRASHIFT 2/4 daratumumab | |
| Candidate Device | HYDRAGEL IF | |
| Predicate Device ( K960669) | ||
| 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. | The HYDRAGEL 1 IF, 2 IF, 4 IF and 9 IF | |
| kits are designed for detection of | ||
| monoclonal proteins in human serum | ||
| and urine by immunofixation | ||
| electrophoresis. The kits are used in | ||
| conjunction with the semi-automated | ||
| HYDRASYS 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 either | ||
| with acid violet or amidoblack. The | ||
| electrophoregrams are evaluated visually | ||
| for the presence of specific reactions | ||
| with the suspect monoclonal proteins. | ||
| Assay Principle | Agarose Gel Electrophoresis | Agarose Gel Electrophoresis |
| Program | Same | Uses IF Program on Hydrasys 2 |
| Reagents | ||
| Gel kit | ||
| Antisera kit | Same | |
| Same | HYDRAGEL IF | |
| Antisera and Fixative for | ||
| immunofixation IF | ||
| NA | ||
| Differences | ||
| Table B | HYDRASHIFT 2/4 daratumumab | |
| Candidate Device | HYDRAGEL IF | |
| Predicate Device K960669) | ||
| Specimen Type | Human Serum | Human Serum, Human Urine |
| Reagents | Using anti-daratumumab antibody | No anti-daratumumab antibody |
| Daratumumab band | Removed from gamma zone into alpha zone | Remains in Gamma zone |
7
Table B. Differences between the predicate device (HYDRAGEL IF) and the candidate device (HYDRASHIFT 2/4 daratumumab) in (Table B).
5. Performance Data:
a) Repeatability
Ten (10) different serum samples, including 1 normal serum sample and 9 serum samples with monoclonal components, were run using the HYDRASHIFT 2/4 daratumumab procedure used in conjunction with each of the following kits: - HYDRAGEL 4 IF Acid violet Standard mask, -HYDRAGEL 4 IF Acid violet Dynamic mask.
Each sample was run 4 times within the same gel.
For each tested sample, all repeats gave 100 % of concordant results within gel.
| Sample No. | Type | Within gel | Total analyses per
gel |
|---------------|--------------------------------|---------------------------|---------------------------|
| Sample No. 1 | Normal | 100% concordant
result | 4 |
| Sample No. 2 | Ig G, L + Ig A, K + Ig
M, L | 100% concordant
result | 4 |
| Sample No. 3 | Ig G, K | 100% concordant
result | 4 |
| Sample No. 4 | Ig G, L | 100% concordant
result | 4 |
| Sample No. 5 | Ig A, K | 100% concordant
result | 4 |
| Sample No. 6 | Ig A, L | 100% concordant
result | 4 |
| Sample No. 7 | 2 Ig M, K | 100% concordant
result | 4 |
| Sample No. 8 | Ig M, L | 100% concordant
result | 4 |
| Sample No. 9 | Kappa free | 100% concordant
result | 4 |
| Sample No. 10 | Lambda free | 100% concordant
result | 4 |
8
b) Reproducibility between gels, between lots and between instruments
Ten (10) different serum samples, including 1 normal serum sample and 9 serum samples with monoclonal components, were run using the HYDRASHIFT 2/4 daratumumab procedure used in conjunction with each of the following kits : - HYDRAGEL 4 IF Acid violet Standard mask, - HYDRAGEL 4 IF Acid violet Dynamic mask.
This study was performed with 3 HYDRASYS 2 instruments and with 3 lots of HYDRASHIFT 2/4 daratumumab kit.
The normal sample was analyzed on 9 runs including one analysis per qel on 3 gels over 3 working days.
The samples with monoclonal components were analyzed on 9 runs with one analysis per gel, over 3 working days.
All samples gave 100 % of concordant results between gels on the 3 HYDRASYS 2 instruments and with 3 lots of HYDRASHIFT 2/4 daratumumab kit.
| Sample
No. | Type | Instrument No. 1 / Lot No. 1 | | | Instrument No. 2 / Lot No. 2 | | | Instrument No. 3 / Lot No. 3 | | | Total analyses
per sample |
|---------------|-----------------------------------|-------------------------------|-------------------------------|-------------------------------|-------------------------------|-------------------------------|-------------------------------|-------------------------------|-------------------------------|-------------------------------|------------------------------|
| | | 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 %
concordant
result | 100 %
concordant
result | 100 %
concordant
result | 100 %
concordant
result | 100 %
concordant
result | 100 %
concordant
result | 100 %
concordant
result | 100 %
concordant
result | 100 %
concordant
result | 27 |
| 2 | Ig G, L +
Ig A, K +
Ig M, L | 100 %
concordant
result | 100 %
concordant
result | 100 %
concordant
result | 100 %
concordant
result | 100 %
concordant
result | 100 %
concordant
result | 100 %
concordant
result | 100 %
concordant
result | 100 %
concordant
result | 9 |
| 3 | Ig G, K | 100 %
concordant
result | 100 %
concordant
result | 100 %
concordant
result | 100 %
concordant
result | 100 %
concordant
result | 100 %
concordant
result | 100 %
concordant
result | 100 %
concordant
result | 100 %
concordant
result | 9 |
| 4 | Ig G, L | 100 %
concordant
result | 100 %
concordant
result | 100 %
concordant
result | 100 %
concordant
result | 100 %
concordant
result | 100 %
concordant
result | 100 %
concordant
result | 100 %
concordant
result | 100 %
concordant
result | 9 |
| 5 | Ig A, K | 100 %
concordant
result | 100 %
concordant
result | 100 %
concordant
result | 100 %
concordant
result | 100 %
concordant
result | 100 %
concordant
result | 100 %
concordant
result | 100 %
concordant
result | 100 %
concordant
result | 9 |
| 6 | Ig A, L | 100 %
concordant
result | 100 %
concordant
result | 100 %
concordant
result | 100 %
concordant
result | 100 %
concordant
result | 100 %
concordant
result | 100 %
concordant
result | 100 %
concordant
result | 100 %
concordant
result | 9 |
| 7 | Ig M, K | 100 %
concordant
result | 100 %
concordant
result | 100 %
concordant
result | 100 %
concordant
result | 100 %
concordant
result | 100 %
concordant
result | 100 %
concordant
result | 100 %
concordant
result | 100 %
concordant
result | 9 |
| 8 | Ig M, L | 100 %
concordant
result | 100 %
concordant
result | 100 %
concordant
result | 100 %
concordant
result | 100 %
concordant
result | 100 %
concordant
result | 100 %
concordant
result | 100 %
concordant
result | 100 %
concordant
result | 9 |
| 9 | Kappa
free | 100 %
concordant
result | 100 %
concordant
result | 100 %
concordant
result | 100 %
concordant
result | 100 %
concordant
result | 100 %
concordant
result | 100 %
concordant
result | 100 %
concordant
result | 100 %
concordant
result | 9 |
| 10 | Lambda
free | 100 %
concordant
result | 100 %
concordant
result | 100 %
concordant
result | 100 %
concordant
result | 100 %
concordant
result | 100 %
concordant
result | 100 %
concordant
result | 100 %
concordant
result | 100 %
concordant
result | 9 |
9
c) External comparative studies
The results presented below have been obtained from 2 external studies performed in the USA. The external study No. 1 was performed on 198 samples and the external study No. 2 was performed on 172 samples. The first 172 samples have been analyzed on both sites.
External study No. 1
Comparative study No. 1 was performed on 198 serum samples analyzed with:
- HYDRAGEL 4 IF Acid Violet Dynamic Mask kit,
- HYDRASHIFT 2/4 daratumumab used in conjunction with HYDRAGEL 4 IF Acid Violet Dvnamic Mask kit.
With the HYDRAGEL 4 IF Acid Violet Dynamic Mask procedure, the daratumumab was visualized on G track and on Kappa track for 113 samples. For those samples, the HYDRASHIFT 2/4 daratumumab used in conjunction with HYDRAGEL 4 IF Acid Violet Dynamic Mask kit allows the shifting of the daratumumab.
For the other 85 samples, the characterization (normal or abnormal with monoclonal components) was the same between both procedures.
This study demonstrated 100 % concordant result:
- For 42 normal serum samples: 100 % concordant result.
- For the 156 pathological serum samples: 100 % concordant result.
External study No. 2
Comparative study No. 2 was performed on 172 serum samples analyzed with:
- HYDRAGEL 4 IF Acid Violet Standard Mask kit, .
- HYDRASHIFT 2/4 daratumumab used in conjunction with HYDRAGEL 4 IF Acid Violet - Standard Mask kit.
With the HYDRAGEL 4 IF Acid Violet Standard Mask procedure, the daratumumab was visualized on G track and on Kappa track for 98 samples, the HYDRASHIFT 2/4 daratumumab used in conjunction with HYDRAGEL 4 IF Acid Violet Standard Mask kit allows the shifting of the daratumumab.
For the other 74 samples, the characterization (normal or abnormal with monoclonal components) was the same between both procedures.
This study demonstrated 100 % concordant result:
- For 38 normal serum samples: 100 % concordant result.
- For the 134 pathological serum samples: 100 % concordant result.
d) Sensitivity
Six (6) serum samples, including 2 normal serum samples and 4 serum samples with different monoclonal components, added with daratumumab at different concentrations (final concentrations in sample between 0.1 and 3.0 g/L) were analyzed with the HYDRASHIFT 2/4 daratumumab 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 daratumumab /anti-daratumumab /anti-daratumumab antibody complex visualized is 0.3 q/L.
e) Controls
It is recommended to run an assayed control serum (such as daratumumab CONTROL, SEBIA PN 4765) after each change of lot of a reagent.
10
f) Interferences
The common interfering factors with the HYDRASHIFT 2/4 daratumumab procedure (bilirubin, triglycerides, hemoglobin and rheumatoid factor) were evaluated in studies based on the Clinical Laboratory Standards Institute (CLSI - USA) EP7-A2 guideline "Interference Testing in Clinical Chemistry; Approved Guideline – Second Edition". Additional inferference studies included: Human Anti-Mouse Antibody (HAMA, Pomalidomide, Lenalidomide, Dexamethasone, Bortezomib).
The results are summarized below
No interference with the HYDRASHIFT 2/4 daratumumab procedure was detected due to the serum sample's concentration of the following interfering factors tested at levels equal to the concentrations listed below :
| Interfering factor | Concentration | Interfering factor/ Drug | Concentration |
|---|---|---|---|
| Bilirubin | 20 mg/dL (342 μM) | Pomalidomide, | 1 mg/L |
| Triglycerides | 3,00 g/dL (34,5 mM) | Lenalidomide | 4 mg/L |
| Hemoglobin | 2 g/L (0,2 g/dL) | Dexamethasone | 1 mg/L |
| Rheumatoid factor | 2000 UI/mL | Bortezomib | 2 mg/L |
| Human Anti-Mouse | |||
| Antibody (HAMA) | Titer : 640 |
q) Results
Interpretation, Interference and Limitations and Troubleshooting: See the instructions for use of the HYDRAGEL IF Standard mask or Dynamic mask kits.
A band on G and K immunofixation tracks outside the gammaqlobulins zone and in alpha-1 zone corresponds to the daratumumab / anti-daratumumab antibody complex. NOTE: Sometimes, the daratumumab complex is more faint in K track than in G track.
The HYDRASHIFT 2/4 daratumumab immunofixation removes the daratumumab lg G, Kappa interference and enables the visual evaluation of the presence or absence of monoclonal proteins on the HYDRAGEL IF kits, a negative test demonstrates the absence of monoclonal proteins in patients who have received daratumumab therapy.
The absence of any monoclonal protein on HYDRASHIFT 2/4 daratumumab immunofixation assay in either Alpha 2. Beta or Gamma zones is interpreted as a neqative assay for monoclonal protein.
The presence of a monoclonal protein ( or biclonal) on HYDRASHIFT 2/4 daratumumab immunofixation assay in either Alpha 2, Beta or Gamma zones is interpreted as a positive assay for monoclonal protein.
Some samples may give a faint band close to the application point due to a non-specific precipitation of proteins. This band may be visible on the G track and more particularly on the K track and cannot be confused with a monoclonal component
11
6. IMWG Response Criteria
The current standard of practice for monitoring responses and relapses in multiple myeloma involve serum protein electrophoresis (SPEP) and Immunofixation (IF) (to determine complete response). International guidelines 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.
NCCN Guidelines Version 3.2017
*The Lancet Oncology 17 Kumar S, Paiva B, Anderson K, et al. International Myeloma Working Group consensus criteria for response and minimal response disease assessment in multiple myeloma, e328-46
| *New criteria (2016) - International Myeloma Working Group | |
|---|---|
| Stringent complete response | Complete response as defined below plus normal FLC |
| ratio** and absence of clonal cells in bone marrow biopsy by | |
| immunohistochemistry (κ/λ ratio ≤4:1 or ≥1:2 for κ and λ | |
| patients, respectively, after counting ≥100 plasma cells)†† | |
| Complete response | Negative immunofixation on the serum and urine and |
| disappearance of any soft tissue plasmacytomas and 10 mg/dL); In patients | |
| without measurable serum and urine M-protein levels and | |
| without measurable involved FLC levels, bone marrow | |
| plasma-cell percentage irrespective of baseline status | |
| (absolute increase must be ≥10%); | |
| Appearance of a new lesion(s), ≥50% increase from nadir in | |
| SPD§§ of >1 lesion, or ≥50% increase in the longest diameter | |
| of a previous lesion >1 cm in short axis; | |
| ≥50% increase in circulating plasma cells (minimum of 200 cells | |
| per µL) if this is the only measure of disease | |
| Clinical relapse | Clinical relapse requires one or more of the following criteria: |
| Direct indicators of increasing disease and/or end organ | |
| dysfunction (calcium elevation, renal failure, anemia, lytic | |
| bone lesions [CRAB features]) related to the underlying clonal | |
| plasma-cell proliferative disorder. It is not | |
| used in calculation of time to progression or progression-free | |
| survival but is listed as something that can be reported | |
| optionally or for use in clinical practice; | |
| Development of new soft tissue plasmacytomas or bone | |
| lesions (osteoporotic fractures do not constitute progression); | |
| Definite increase in the size of existing plasmacytomas or bone | |
| lesions. A definite increase is defined as a 50% | |
| (and ≥1 cm) increase as measured serially by the SPD§§ of the | |
| measurable lesion; | |
| Hypercalcemia (>11 mg/dL); | |
| Decrease in hemoglobin of ≥2 g/dL not related to therapy or | |
| other non-myeloma-related conditions; | |
| Rise in serum creatinine by 2 mg/dL or more from the start of | |
| the therapy and attributable to myeloma; Hyperviscosity | |
| related to serum paraprotein |
12
13
7. Conclusion:
The submitted information in this premarket notification is complete and supports a substantial equivalence decision.