Predicate Devices

Reference Devices

Not Found

AI/ML (Artificial Intelligence / Machine Learning)

No
The document describes a semi-automated electrophoresis system and a chemical kit for immunofixation, with visual evaluation of results. There is no mention of AI or ML in the device description, intended use, or performance studies.

Therapeutic

No
This device is an in vitro diagnostic (IVD) product used for the qualitative detection of monoclonal proteins in human serum, specifically designed to mitigate interference from isatuximab IgG kappa. It is used for diagnostic purposes (to identify or confirm the presence of monoclonal gammopathies) rather than for treating or preventing a disease, which is the definition of a therapeutic device.

Diagnostic

Yes

The device qualitatively detects monoclonal proteins in human serum, which is used to diagnose monoclonal gammopathies.

SaMD (Software as a Medical Device)

No

The device described is a kit containing reagents (HYDRASHIFT 2/4 isatuximab kit) used in conjunction with a semi-automated electrophoresis apparatus (HYDRASYS 2) and other kits (HYDRAGEL IF kit). While the process involves visual evaluation of electropherograms, the core components are physical reagents and hardware, not software.

IVD (In Vitro Diagnostic)

Yes, this device is an IVD (In Vitro Diagnostic).

The document explicitly states: "For In Vitro Diagnostic use." in the "Intended Use / Indications for Use" section and again in the "Intended User / Care Setting" section.

Furthermore, the intended use describes the qualitative detection of monoclonal proteins in human serum, which is a diagnostic test performed on a biological sample outside of the body. This aligns with the definition of an In Vitro Diagnostic device.

PCCP (Predetermined Change Control Plan) Authorized

N/A

Overview

Intended Use / 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 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.

Product codes (comma separated list FDA assigned to the subject device)

CFF

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.

Isatuximab 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.

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

Not Found

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 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.

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.

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.

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.

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 conjunction 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.

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 conjunction with HYDRAGEL 4 IF Acid Violet Standard Mask kit allows the shifting of the isatuximab.

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.

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.

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.

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:

Unconjugated bilirubin: 20 mg/dL (342 micro M)
Conjugated bilirubin: 20 mg/dL (342 micro 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

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:

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

Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)

Sensitivity: The detection limit of isatuximab and / or isatuximab / anti-isatuximab antibody complex visualized is 0.3 g/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.

K960669

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

Regulation Number and Section

§ 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).

Summary

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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

1

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

2

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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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
Address	1705 Corporate Drive Suite 400
Norcross, Georgia 30093, USA
Contact	Karen Anderson, Dir of Regulatory
Phone: 1-800-835-6497
Fax: 770-446-8511
Email: karen.anderson@sebia-usa.com
Matthew Wagner, Ph.D.
Scientific Affairs Specialist
Phone: 1-800-835-6497
Email: matthew.wagner@sebia-usa.com
Date Prepared	November 9, 2021
Manufacturing	Sebia
Parc Technologique Léonard de Vinci
Rue Léonard 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 isatuximab
Common Name	Hydrashift isatuximab Serum Immunofixation
Product Regulation No.	21CFR sec. 866.5510

4

Product Codes	CFF
Device classification and Panel
Classification	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 to
use)	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 IF
Acid violet - Dynamic mask	4302, 4304 or 4381*
Antisera and Fixative for immunofixation IF -
Dynamic mask
or	4315

5

| HYDRAGEL 2 or 4 IF

Acid violet - Standard mask	4802, 4804 or 4881*
Antisera and Fixative for immunofixation IF
Standard 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 or
2MERCAPTOETHANOL)	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 Device
510(k) number | Product Code | Regulation No |
|-----------------------|-----------------------------------|--------------|---------------|
| HYDRAGEL IF | K960669 | CFF | 866.5510 |

6

Similarities between the candidate device (HYDRASHIFT 2/4 isatxumiab) and the predicate device (HYDRAGEL IF) (Table A).

Similarities
Table A	HYDRASHIFT 2/4 isatuximab
Candidate Device	HYDRAGEL IF
Predicate Device
K960669
Intended
Use /
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 IgG 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.	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
Software
Program	Same	IF Program

7

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 isatuximab
Candidate Device	HYDRAGEL IF
Predicate Device K960669
Specimen Type	Human Serum	Human Serum, Human Urine
Reagents	Using anti-isatuximab antibody	No anti-isatuximab antibody
isatuximab
band	Removed from gamma zone into
alpha 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

8

| Sample No. 7 | IgM kappa | 100% concordant
result | 4 |
|---------------|---------------------------|---------------------------|---|
| Sample No. 8 | IgM lambda +
IgA kappa | 100% concordant
result | 4 |
| Sample No. 9 | Kappa Free | 100% concordant
result | 4 |
| Sample No. 10 | Lambda free | 100% concordant
result | 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.

| Sample
No. | Type | Instrument No. 1/
Kit lot No. 1 | | | Instrument No. 2/
Kit lot No. 2 | | | Instrument No. 3/
Kit 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 | |
| 2 | 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 | 9 |
| 3 | IgG
kappa | 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 | IgG
lambda | 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 | IgA
kappa | 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 | IgA
lambda | 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 | IgM
kappa | 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 | IgM
lambda +
IgA
kappa | 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

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.

| Sample
No. | Type | Instrument No. 1 /
Kit No. 1 | | | Instrument No. 2 /
Kit No. 2 | | | Instrument No. 3 /
Kit 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 |

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 serum
samples |
|------------------|----------------------------|
| 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

10

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.

11

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 + 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	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.

12

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:

13

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.