HYDRASHIFT 2/4 daratumumab

K190851 · Sebia · CFF · May 2, 2019 · Immunology

Device Facts

• Record ID: K190851
• Device Name: HYDRASHIFT 2/4 daratumumab
• Applicant: Sebia
• Product Code: CFF · Immunology
• Decision Date: May 2, 2019
• Decision: SESE
• Submission Type: Special
• Regulation: 21 CFR 866.5510
• Device Class: Class 2

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.

Device Story

In vitro diagnostic test; detects daratumumab in human serum; utilizes anti-daratumumab total immunoglobulins; raw material source transitioned from murine to Chinese hamster ovary (CHO) cells; used in clinical laboratory settings by trained personnel; results assist in monitoring or identifying presence of therapeutic monoclonal antibody; modification maintains fundamental scientific technology of original cleared device (K172195).

Clinical Evidence

Bench testing only. Performance studies included concordance, sensitivity, and stability testing to validate the impact of the raw material source change from murine to Chinese hamster ovary cells.

Technological Characteristics

In vitro diagnostic assay; utilizes anti-daratumumab total immunoglobulins derived from Chinese hamster ovary cells; qualitative detection method; performance characteristics verified via concordance, sensitivity, and stability testing.

Indications for Use

Indicated for qualitative detection of monoclonal proteins in human serum via immunofixation electrophoresis in patients receiving daratumumab therapy to mitigate daratumumab-induced interference.

Regulatory Classification

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.

Predicate Devices

• HYDRASHIFT 2/4 daratumumab test (K172195)

Submission Summary (Full Text)

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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 ([e-mail]) or phone [phone] 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)

| <span></span> | <input checked="true" type="checkbox"/> Prescription Use (Part 21 CFR 801 Subpart D) |
|---------------|--------------------------------------------------------------------------------------|
| <span></span> | <input type="checkbox"/> 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 400<br>Norcross, Georgia 30093, USA |
| Contact | Karen Anderson, Dir of Technical and Regulatory<br>Phone: [phone]<br>Fax: [phone]<br>Email: [e-mail]<br>Matthew C. Wagner, Ph.D<br>Scientific Affairs Specialist<br>Phone: [phone]<br>Email: [e-mail] |
| Date Prepared | March 5, 2019 |
| Manufacturing | Sebia<br>Parc Technologique L\u00e9onard de Vinci<br>Rue L\u00e9onard de Vinci,<br>CP 8010 LISSES, 91008 EVRY Cedex<br>FRANCE<br>Phone: [phone]<br>Fax: [phone] |
| 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 Panel<br>Classification | Class II , Immunology (82) |
| Establishment Registration No. | 8023024 |
| Predicate Devices | The candidate device is a modification of the<br>predicate device. The device name , HYDRASHIFT<br>2/4 daratumumab, is unchanged from how it was<br>cleared 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 Comparison<br>Item | HYDRASHIFT 2/4 daratumumab<br>Predicate Device (K172195) | HYDRASHIFT 2/4 daratumumab<br>Candidate/Modified<br>Device |
|-----------------------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|------------------------------------------------------------|
| 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 (<br>IF) test kits used<br>in conjuction with<br>the HYDRASHIFT<br>2/4 daratumumab | HYDRAGEL 4 IF Acid violet<br>Standard mask,<br>HYDRAGEL 4 IF Acid violet<br>Dynamic mask. | Same |
|----------------------------------------------------------------------------------------------------|----------------------------------------------------------------------------------------------------------------------------|------|
| Scientific<br>Technology | Agarose Gel Electrophoresis | Same |
| Specimen Type | Serum | Same |
| Results | Qualitative | Same |
| Sensitivity/ Lowest detectable<br>daratumumab limit | The detection limit of daratumumab<br>and / or daratumumab / anti-<br>daratumumab antibody<br>complexvisualized is 0.3 g/L | Same |
| Efficiency ( Maximum removal of<br>complex) | 3.0 g/L | Same |
| Daratumumab<br>band<br>when<br>HYDRASHIFT<br>treated<br>with<br>daratumumab kit | Removed from gamma zone into<br>alpha zone | Same |
| Stability of the anti-daratumumab<br>reagent<br>Stability 2 to 8ºC | 2 years | Same |
| daratumumab Control | daratumumab control (K172195) | Same |

Table 2: Assay Comparison, Labelled Performance Characteristics

| Item | HYDRASHIFT 2/4 daratumumab<br>Predicate Device (K172195) | HYDRASHIFT 2/4 daratumumab<br>Candidate/Modified Device |
|----------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Package Insert<br>Labeling | The anti-daratumumab<br>antiserum is ready to use.<br>It contains murine anti-<br>daratumumab total<br>immunoglobulins.<br>For easy identification of the<br>antiserum and as an aid in<br>monitoring its application, the<br>antiserum is colored with distinct<br>nonhazardous dye that matches<br>the color of the vial label. | The anti-daratumumab antiserum is<br>ready to use. It contains anti-<br>daratumumab total immunoglobulins<br>from Chinese hamster ovary cells. For<br>easy identification of the antiserum and<br>as an aid in monitoring its application, the<br>antiserum is colored with distinct<br>nonhazardous dye that matches the color<br>of 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.