Predicate Devices

Reference Devices

Not Found

AI/ML (Artificial Intelligence / Machine Learning)

No
The device description details a standard ELISA procedure and calculation based on a calibration curve, with no mention of AI or ML technologies.

Therapeutic

No
The device is an in vitro diagnostic (IVD) kit used for the "quantification of Kappa/Lambda free light chains in human serum" to aid in the "diagnosis and monitoring of multiple myeloma and AL amyloidosis." It does not provide therapy but rather information for diagnosis and monitoring.

Diagnostic

Yes
The document states that the device "aids in the diagnosis and monitoring of multiple myeloma and AL amyloidosis" and is for "In Vitro Diagnostic Use only."

SaMD (Software as a Medical Device)

No

The device description clearly outlines a physical ELISA kit with reagents and a multi-step laboratory procedure involving incubation, washing, and spectrophotometry. While calculation of results involves software, the core device is a hardware-based in vitro diagnostic kit.

IVD (In Vitro Diagnostic)

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

Here's why:

Explicit Statement: The "Intended Use / Indications for Use" section clearly states: "For In Vitro Diagnostic Use only."
Nature of the Test: The device is a kit designed to quantify specific substances (free light chains) in human serum, which is a biological sample taken from the body. This is a hallmark of in vitro diagnostics.
Purpose: The measurement of free light chains is stated to "aid in the diagnosis and monitoring of multiple myeloma and AL amyloidosis." This indicates a medical purpose for the test results.
Methodology: The description details an ELISA procedure, which is a common laboratory technique used for in vitro diagnostic testing.
Intended User: The "Intended User / Care Setting" section states "For In Vitro Diagnostic Use only. For prescription use only," further reinforcing its IVD nature.

All these points align with the definition of an In Vitro Diagnostic device, which is a medical device intended for use in vitro for the examination of specimens derived from the human body solely or principally for the purpose of providing information concerning a physiological or pathological state, or a congenital abnormality, or to determine the compatibility of tissues or organs, or to monitor therapeutic measures.

PCCP (Predetermined Change Control Plan) Authorized

N/A

Overview

Intended Use / Indications for Use

The FLC Kappa kit is intended for the quantification of Kappa free light chains in human serum from adults with an Enzyme-Linked Immunosorbent Assay (ELISA) procedure. Measurement of free light chains aids in the diagnosis and monitoring of multiple myeloma and AL amyloidosis. It must be used in conjunction with other laboratory and clinical findings.

For In Vitro Diagnostic Use only.

The FLC Lambda kit is intended for the quantification of Lambda free light chains in human serum from adults with an Enzyme-Linked Immunosorbent Assay (ELISA) procedure. Measurement of free light chains aids in the diagnosis and monitoring of multiple myeloma and AL amyloidosis. It must be used in conjunction with other laboratory and clinical findings.

For In Vitro Diagnostic Use only.

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

DFH, DEH

Device Description

The FLC Kappa and FLC Lambda test kits are intended for the quantification of free light chains in human serum from adults with an Enzyme-Linked Immunosorbent Assay (ELISA) procedure utilizing specific antibodies targeting anti-Lambda free light chains.

It is carried out in 8 successive steps:

Incubation of the previously diluted samples and calibrators, in the wells of the microplate, i where specific free light chain antibodies are fixed.
Washing of the wells to remove elements that have not been fixed by the anti-free light chain i antiserum.
Incubation with an anti- light chain antiserum (Kit specific) conjugated to peroxidase. i
Washing of the wells to remove the excess of antiserum conjugated to peroxidase.
Incubation with peroxidase substrate.
Stopping of the enzymatic reaction with an acidic solution. i
Reading of the optical density by absorbance spectrophotometry at 450 nm of the colored i product.
Calculation of the free light chain concentration of the sample using a calibration curve obtained with calibrators that have been analyzed on the same microplate.

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

adults

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) Clinical Study: Monitoring of multiple myeloma and AL amyloidosis

Multiple myeloma:
Sample size: A total of 551 follow up samples from 235 unique subjects diagnosed with multiple myeloma and with expanded racial and ethnic diversity (Caucasian, African American, Hispanic, Asian).
Key results: The concordance of the results obtained with FLC Kappa and FLC Lambda kits for monitoring the Multiple Myeloma with other tests and clinical assessment was evaluated based on criteria of the IMWG (International Myeloma Working Group). Overall concordance was 90.4% (498/551, 95% CI: 87.9%; 92.8%).

AL-amyloidosis:
Sample size: A total of 190 follow up samples from 87 unique subjects diagnosed with AL-Amyloidosis and with expanded racial and ethnic diversity (Caucasian, African American, Hispanic).
Key results: The concordance of the results obtained with FLC Kappa and FLC Lambda kits for monitoring the AL-Amyloidosis with other tests and clinical assessment was evaluated based on the consensus guideline for assessment of treatment response published by Comenzo et al., 2012, reiterated by Palladini et al., 2012 and updated in 2021 (Mode No. 1), and published by Kumar et al., 2022 as the National Comprehensive Cancer Network (NCCN) guidelines for AL-Amyloidosis (Mode No. 2).
For Evaluation Mode No. 1, overall concordance was 71.1% (135/190, 95% CI: 64.6%; 77.5%).
For Evaluation Mode No. 2, overall concordance was 64.7% (123/190, 95% CI: 57.9%; 71.5%).

b) Stability:
Shelf-life studies were conducted for FLC Kappa and FLC Lambda kits and FLC controls Level 1 and Level 2. All results met stability acceptance criteria and product stability claims.

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

Multiple myeloma monitoring (Progression vs No Progression):
Clinical Sensitivity: 68.3% (28/41) (95% CI: 54.0%; 82.5%)
Clinical Specificity: 94.2% (310/329) (95% CI: 91.7%; 96.7%) for Stable Disease

For the monitoring events regarding "Progression" and "No-progression" based on IMWG criteria:
Clinical Sensitivity for Progression: Not explicitly stated, as the table shows Progression (28) and No Progression (13) which sum up to 41, and No-Progression (6) and Progression (504) which sum up to 510. The 28/41 (68.3%) refers to IMWG Progression-FLC Progression in the first table, not clinical sensitivity directly.
The table in "The clinical sensitivity and specificity for the monitoring events regarding "Progression" and "Noprogression" based on criteria of the IMWG were evaluated with FLC Kappa and Lambda kits" states:
Progression (FLC Assays) / Progression (Clinical Assessment): 28
No Progression (FLC Assays) / No Progression (Clinical Assessment): 504
Total Clinical Progression: 41
Total Clinical No Progression: 510

AL-amyloidosis monitoring (Progression vs No Progression) based on Evaluation mode No. 1 and No. 2:
Clinical Sensitivity: 68.2% (15/22) (95% Cl: 48.7% to 87.6%)
Clinical Specificity: 98.8% (166/168) (95% Cl: 97.2% to 100.0%)

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.

K031016

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

§ 866.5550 Immunoglobulin (light chain specific) immunological test system.

(a)
Identification. An immunoglobulin (light chain specific) immunological test system is a device that consists of the reagents used to measure by immunochemical techniques both kappa and lambda types of light chain portions of immunoglobulin molecules in serum, other body fluids, and tissues. In some disease states, an excess of light chains are produced by the antibody-forming cells. These free light chains, unassociated with gamma globulin molecules, can be found in a patient's body fluids and tissues. Measurement of the various amounts of the different types of light chains aids in the diagnosis of multiple myeloma (cancer of antibody-forming cells), lymphocytic neoplasms (cancer of lymphoid tissue), Waldenstrom's macroglobulinemia (increased production of large immunoglobulins), and connective tissue diseases such as rheumatoid arthritis or systemic lupus erythematosus.(b)
Classification. Class II (performance standards).

Summary

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, with the letters "FDA" in a blue square. To the right of the blue square is the text "U.S. FOOD & DRUG ADMINISTRATION" in blue.

February 23, 2024

Sebia Karen Anderson Director of Regulatory Affairs and Ouality Assurance 1705 Corporate Drive Suite 400 Norcross, Georgia 30093

Re: K231601

Trade/Device Name: FLC Kappa, FLC Lambda Regulation Number: 21 CFR 866.5550 Regulation Name: Immunoglobulin (Light Chain Specific) Immunological Test System Regulatory Class: Class II Product Code: DFH, DEH Dated: January 12, 2024 Received: January 12, 2024

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 (the 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 available 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.

Additional information about changes that may require a new premarket notification are provided in the FDA guidance documents entitled "Deciding When to Submit a 510(k) for a Change to an Existing Device"

1

K231601 - Karen Anderson

(https://www.fda.gov/media/99812/download) and "Deciding When to Submit a 510(k) for a Software Change to an Existing Device" (https://www.fda.gov/media/99785/download).

Your device is also subject to, among other requirements, the Quality System (QS) regulation (21 CFR Part 820), which includes, but is not limited to, 21 CFR 820.30, Design controls; 21 CFR 820.90, Nonconforming product; and 21 CFR 820.100. Corrective and preventive action. Please note that regardless of whether a change requires premarket review. the OS regulation requires device manufacturers to review and approve changes to device design and production (21 CFR 820.30 and 21 CFR 820.70) and document changes and approvals in the device master record (21 CFR 820.181).

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 Part 803) for devices or postmarketing safety reporting (21 CFR Part 4, Subpart B) for combination products (see https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safetyreporting-combination-products); 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 Part 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR Parts 1000-1050.

Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR 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 -S

Ying Mao, Ph.D. Branch Chief Division of Immunology and Hematology Devices OHT7: Office of In Vitro Diagnostics Office of Product Evaluation and Quality Center for Devices and Radiological Health

2

Indications for Use

510(k) Number (if known) K231601

Device Name FLC Kappa FLC Lambda

Indications for Use (Describe)

The FLC Kappa kit is intended for the quantification of Kappa free light chains in human serum from adults with an Enzyme-Linked Immunosorbent Assay (ELISA) procedure. Measurement of free light chains aids in the diagnosis and monitoring of multiple myeloma and AL amyloidosis. It must be used in conjunction with other laboratory and clinical findings.

For In Vitro Diagnostic Use only.

The FLC Lambda kit is intended for the quantification of Lambda free light chains in human serum from adults with an Enzyme-Linked Immunosorbent Assay (ELISA) procedure. Measurement of free light chains aids in the diagnosis and monitoring of multiple myeloma and AL amyloidosis. It must be used in conjunction with other laboratory and clinical findings.

For In Vitro Diagnostic 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)

CONTINUE ON A SEPARATE PAGE IF NEEDED.

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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 Regulatory, Sebia Inc.
Phone: 1-800-835-6497
Fax: 770-446-8511
Email: karen.anderson@sebia-usa.com

Matthew C Wagner, Scientific Affairs Specialist
Phone 1-800-835-6497, 3752
Fax 770-446-8511
Email: matthew.wagner@sebia-usa.com |
| Date Prepared | February 16, 2024 |
| 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 | FLC Kappa
FLC Lambda |
| Common Name | Light Chain immunological test system |
| Product Regulation No. | 21CFR sec. 866.5550 - Immunoglobulin (light chain
specific) immunological test system

4

1. DEVICE DESCRIPTIONS

The FLC Kappa and FLC Lambda test kits are intended for the quantification of free light chains in human serum from adults with an Enzyme-Linked Immunosorbent Assay (ELISA) procedure utilizing specific antibodies targeting anti-Lambda free light chains.

It is carried out in 8 successive steps:

Incubation of the previously diluted samples and calibrators, in the wells of the microplate, i where specific free light chain antibodies are fixed.
Washing of the wells to remove elements that have not been fixed by the anti-free light chain i antiserum.
Incubation with an anti- light chain antiserum (Kit specific) conjugated to peroxidase. i
Washing of the wells to remove the excess of antiserum conjugated to peroxidase.
Incubation with peroxidase substrate. ।
Stopping of the enzymatic reaction with an acidic solution. i
Reading of the optical density by absorbance spectrophotometry at 450 nm of the colored i product.
। Calculation of the free light chain concentration of the sample using a calibration curve obtained with calibrators that have been analyzed on the same microplate.

The devices in this submission are not materially changed from cleared under K210623. The purpose for this submission is to:

add aids in the monitoring of Multiple Myeloma and Immunoglobulin Light-Chain (AL-) amyloidosis to the intended use,
extend shelf-life for FLC Kappa and FLC Lambda kits,
add additional data for shelf-life of FLC Controls Level 1 and Level 2.

2. REAGENTS

REAGENTS AND MATERIALS SUPPLIED IN THE FLC KAPPA AND FLC LAMBDA KITS

| ITEMS | PN 5102
FLC Kappa Kit | PN 5103
FLC Lambda Kit |
|------------------------------------------------------------|---------------------------------------------------------------|----------------------------------------------------------------|
| Microplate Kappa 1 plate with 12
segments, 8 wells each | Microplate Kappa 1 plate with 12 segments, 8 wells each | Microplate Lambda 1 plate with 12 segments, 8 wells each |
| Dilution buffer (ready to use) | 1 vial, 100 mL | 1 vial, 100 mL |
| Wash solution (stock solution) | 1 vial, 100 mL | 1 vial, 100 mL |
| Calibrators (ready to use) | 5 vials, 0.6 mL each
Kappa Calibrators | 5 vials, 0.6 mL each
Lambda Calibrators |
| PER antiserum (ready to use) | 1 vial, 12 mL
Anti-Kappa - PER
antiserum (ready to use) | 1 vial, 12 mL
Anti-Lambda – PER
antiserum (ready to use) |
| Substrate | 1 vial, 12 mL
Substrate Kappa (ready to
use) | 1 vial, 12 mL
Substrate Lambda (ready
to use) |
| Stop solution (ready to use) | 1 vial, 12 mL | 1 vial, 12 mL |

5

REAGENTS/SUPPLIES REQUIRED BUT NOT SUPPLIED IN THE KITS

SUPPLIES	SEBIA PRODUCT NUMBER
Densitometer for microplate reading by
absorbance spectrophotometry at 450 nm.
NON COATED ELISA PLATES (10), SEBIA,
microplates with scored wells in order to
complete segments when the forecasted
number of samples per segment is fewer than
8, and frame
to store the segments that have not been
used.	PN 5303
Absorbent paper for removal the excess of
wash solution from the wells of the microplate.
Multichannel pipette.
FLC CONTROL LEVEL 1	PN 5112
FLC CONTROL LEVEL 2	PN 5113

3. INDICATIONS FOR USE

FLC Kappa and FLC Lambda kits

The FLC Kappa kit is intended for the quantification of Kappa free light chains in human serum from adults with an Enzyme-Linked Immunosorbent Assay (ELISA) procedure. Measurement of free light chains aids in the diagnosis and monitoring of multiple myeloma and AL amyloidosis. It must be used in coniunction with other laboratory and clinical findings. For In Vitro Diagnostic Use only.

The FLC Lambda kit is intended for the quantification of Lambda free light chains in human serum from adults with an Enzyme-Linked Immunosorbent Assay (ELISA) procedure. Measurement of free light chains aids in the diagnosis and monitoring of multiple myeloma and AL amyloidosis. It must be used in conjunction with other laboratory and clinical findings. For In Vitro Diagnostic Use only.

Special conditions for use statements: For prescription use only.

Warning: The result of the FLC Kappa and FLC Lambda in a given specimen determined with assays and/or instrument platforms from different manufacturers can vary due to differences in assay methods and reagent

specificity. The results reported by the laboratory to the physician must include the identity of the assay used. Values obtained with different assay methods cannot be used interchangeably. If, in the course of serially monitoring a patient, the assay method used for determining the FLC Kappa level is changed, additional sequential testing should be carried out. Prior to changing assays, the laboratory MUST confirm baseline values for patients being serially monitored.

6

SUBSTANTIAL EQUIVALENCE INFORMATION

Predicate Device Name	Predicate 510(k) number	Regulation No.
The Binding Site Freelite®
Human Kappa Free Kit for use on
the Siemens BN™ II	K031016	866.5550
The Binding Site Freelite®
Human Lambda Free Kit for use
on the Siemens BN™ II	K031016	866.5550

4. COMPARISON WITH PREDICATE DEVICE

Kit Similarities (Table A).

Similarities

| Table A | Candidate Device
FLC Kappa
FLC Lambda | Predicate
The Binding Site Freelite® Human Kappa Free
and Freelite® Human Lambda Free kits for use
on the Siemens BN™ II (K031016) |
|-------------|---------------------------------------------|---------------------------------------------------------------------------------------------------------------------------------------------|
| Analyte | Kappa: Kappa FLC
Lambda: Lambda FLC | Same |
| Measurement | Quantitative | Same |

Kit Differences (Table B)

	Differences
Table B	Candidate Device	Predicate Device
Indications for Use	The FLC Kappa kit is intended for the
quantification of Kappa free light chains in
human serum from adults with an
Enzyme-Linked Immunosorbent Assay
(ELISA) procedure. Measurement of free
light chains aids in the diagnosis and
monitoring of multiple myeloma and AL
amyloidosis. It must be used in
conjunction with other laboratory and
clinical findings.
For In Vitro Diagnostic Use only.
Special conditions for use statements:
For prescription use only.	Kappa: This kit is intended for the
quantitation of kappa free light chains in
serum and urine on the Siemens BN™ II.
Measurement of free light chains aids in the
diagnosis and monitoring of multiple
myeloma, lymphocytic neoplasms,
Waldenstrom's macroglobulinemia, AL
amyloidosis, light chain deposition disease
and connective tissue diseases such as
systemic lupus erythematosus in
conjunction with other laboratory and
clinical findings
	The FLC Lambda kit is intended for the
quantification of Lambda free light chains
in human serum from adults with an
Enzyme-Linked Immunosorbent Assay
(ELISA) procedure. Measurement of free
light chains aids in the diagnosis and
monitoring of multiple myeloma and AL
amyloidosis. It must be used in
conjunction with other laboratory and
clinical findings.
For In Vitro Diagnostic Use only
Special conditions for use statements:
For prescription use only..	Lambda: This kit is intended for the
quantitation of lambda free light chains in
serum and urine on the Siemens BN TM II.
Measurement of free light chains aids in
the diagnosis and monitoring of multiple
myeloma, lymphocytic neoplasms,
Waldenstrom's macroglobulinemia, AL
amyloidosis, light chain deposition
disease and connective tissue diseases
such as systemic lupus erythematosus in
conjunction with other laboratory and
clinical findings.
Specimen Type	Human Serum	Human Serum, Human Urine
Detection Method	Enzyme-Linked Immunosorbent
Assay (ELISA)	Nephelometric
Detection Antibody	Kappa : Sandwich ELISA with polyclonal
rabbit anti- human kappa free light chains
coated on the well of the microplate
(capture antibody) and polyclonal rabbit
anti-human kappa light chain conjugated
to horseradish peroxidase (HRP)
(detection antibody)	Kappa: Polyclonal sheep anti-human
kappa antibody coated with latex
particles
	Lambda: Sandwich ELISA with polyclonal
rabbit anti-human lambda free light chain
coated on the well of the microplate
(capture antibody) and polyclonal rabbit
anti-human lambda light chain
conjugated to horseradish
peroxidase (HRP) (detection antibody)	Lambda: Polyclonal sheep anti-human
Lambda antibody coated with latex
particles
Analytical Measuring ranges	Kappa
Standard dilution (1/1000)
4.5 to 76.2 mg/L
(dilution scheme 1/250 to 1/100 000)	Kappa
Standard dilution (1/100)
5.9 to 190 mg/L
(dilution scheme 1/5 to 1/8000)
	Lambda
Standard dilution (1/1000)
3.8 to 66.8 mg/L
(dilution scheme 1/250 to 1/100 000)	Lambda
Standard dilution (1/100)
5.0 to 160 mg/L
(dilution scheme 1/5 to 1/8000)
Reference Interval	Kappa: 6.4 to 17.4 mg/L.
Lambda: 8.4 to 21.8 mg/L.
Ratio: 0.46 to 1.51	Kappa: 3.30 to 19.40 mg/L
Lambda: 5.71 to 26.30 mg/L
Ratio: 0.26-1.65

7

8

Calibrators:

Similarities
Item	Candidate	Predicate
Reference Material	Internal Reference preparation	Same

Differences
Item	Candidate	Predicate
Number of levels	5	One

PERFORMANCE DATA 5.

Performance Data:

Extended indication for aids in the monitoring of multiple myeloma and AL amyloidosis. Extended shelf-life for FLC Kappa and FLC Lambda kits and additional data for shelf-life of FLC controls Level 1 and Level 2.

See submissions K210623 for previously documented analytical and clinical studies: Precision and Reproducibility Linearity/assay Limit of Blank (LOB) / Limit of Detection (LOD) / Limit of Quantitation (LOQ) Hook Effect (Antigen Excess) Traceability Analytical specificity: Biological and Drug Interferences In-use Stability Expected values/ Reference range Comparison studies: Quantitative and Qualitative comparison Clinical Study: Diagnosis of multiple myeloma and AL amyloidosis

a)Clinical Study

Monitoring of multiple myeloma and AL amyloidosis

Multiple myeloma

A total of 551 follow up samples from 235 unique subjects diagnosed with multiple myeloma and with expanded racial and ethnic diversity (Caucasian, African American, Hispanic, Asian) were included in the clinical study for FLC Kappa and FLC Lambda assays.

The concordance of the results obtained with FLC Kappa and FLC Lambda kits for monitoring the Multiple Myeloma with other tests and clinical assessment was evaluated based on criteria of the IMWG (International Myeloma Working Group).

9

The obtained results are as follows:

Response based	Clinical Assessment
on FLC Assays	Good
Response*	Moderate
Response**	Stable Disease
(SD)	Progressive
Disease (PD)	Total
Good Response*	78	0	0	1	79
Moderate
Response**	0	82	14	0	96
Stable Disease
(SD)	0	20	310	12	342
Progressive
Disease (PD)	0	1	5	28	34
Total	78	103	329	41	551
Concordance	100.0%	79.6%	94.2%	68.3%	90.4%
(n/N)	(78/78)	(82/103)	(310/329)	(28/41)	(498/551)
(95% CI)	(100.0%;
100.0%)	(71.8%;
87.4%)	(91.7%;
96.7%)	(54.0%;
82.5%)	(87.9%;
92.8%)

Including subjects with Stringent Complete Response (sCR) and Complete Response (CR). ** Including subjects with Very Good Partial Response (VGPR) and Partial Response (PR).

The clinical sensitivity and specificity for the monitoring events regarding "Progression" and "Noprogression" based on criteria of the IMWG were evaluated with FLC Kappa and Lambda kits. The obtained results are as follows:

| Response based on

FLC Assays	Clinical Assessment
	Progression	No Progression	Total
Progression*	28	6	34
No Progression**	13	504	517
Total	41	510	551

Progression (PD- Progressive Disease): (≥ 25% increase of M-protein AND increase of M-protein ≥ 0.5 g/L) OR (≥ 25% increase of rd dFLC AND d dFLC increase > 100 mg/L). ** No Progression: all other cases.

AL-amyloidosis

A total of 190 follow up samples from 87 unique subjects diagnosed with AL-Amyloidosis and with expanded racial and ethnic diversity (Caucasian, African American, Hispanic) were included in the clinical study for FLC Kappa and FLC Lambda assays.

The concordance of the results obtained with FLC Kappa and FLC Lambda kits for monitoring the AL-Amyloidosis with other tests and clinical assessment was evaluated based on the consensus guideline for assessment of treatment response published by Comenzo et al., 2012, reiterated by Palladini et al., 2012 and updated in 2021 (Mode No. 1), and published by Kumar et al., 2022 as the National Comprehensive Cancer Network (NCCN) guidelines for AL-Amyloidosis (Mode No. 2).

10

The obtained results are as follows:

| Response based on

FLC Assays	Clinical Assessment (Evaluation mode No. 1)
	Complete
Response
(CR)	Very Good
Partial
Response
(VGPR)	Partial
Response
(PR)	Stable Disease
/ No Response
(SD/NR)	Progressive
Disease (PD)	Total
Complete Response
(CR)	17	2	2	0	1	22
Very Good Partial
Response (VGPR)	4	74	14	14	2	108
Partial Response (PR)	1	2	9	1	2	15
Stable Disease /
No Response (SD/NR)	0	2	4	20	2	28
Progressive Disease
(PD)	0	2	0	0	15	17
Total	22	82	29	35	22	190
Concordance
(n/N)
(95% CI)	77.3%
(17/22)
(59.8%;
94.8%)	90.2%
(74/82)
(83.8%;
96.7%)	31.0%
(9/29)
(14.2%;
47.9%)	57.1%
(20/35)
(40.7%; 73.5%)	68.2%
(15/22)
(48.7%;
87.6%)	71.1%
(135/190)
(64.6%;
77.5%)

| Response based on

FLC Assays	Clinical Assessment (Evaluation mode No. 2)
	Complete
Response
(CR)	Very Good
Partial
Response
(VGPR)	Partial
Response
(PR)	Stable Disease
/ No Response
(SD/NR)	Progressive
Disease (PD)	Total
Complete Response
(CR)	6	8	2	0	0	16
Very Good Partial
Response (VGPR)	9	73	14	15	3	114
Partial Response
(PR)	0	3	9	1	2	15
Stable Disease /
No Response
(SD/NR)	0	2	4	20	2	28
Progressive Disease
(PD)	0	2	0	0	15	17
Total	15	88	29	36	22	190
Concordance
(n/N)
(95% CI)	40.0%
(6/15)
(15.2%;
64.8%)	83.0%
(73/88)
(75.1%;
90.8%)	31.0%
(9/29)
(14.2%;
47.9%)	55.6%
(20/36)
(39.3%; 71.8%)	68.2%
(15/22)
(48.7%;
87.6%)	64.7%
(123/190)
(57.9%;
71.5%)

11

The clinical sensitivity and specificity for the monitoring events regarding "Progression" and "Noprogression" based on evaluation modes No. 1 and No. 2 were evaluated with FLC Kappa and Lambda kits. The obtained results are as follows:

| Response based on

FLC Assays	Clinical Assessment (Evaluation mode No. 1)
	Progression	No Progression	Total
Progression*	15	2	17
No Progression**	7	166	173
Total	22	168	190

Clinical Sensitivity: 68.2% (15/22) (95% Cl: 48.7% to 87.6%) Clinical Specificity: 98.8% (166/168) (95% Cl: 97.2% to 100.0%)

| Response based on

FLC Assays	Clinical Assessment (Evaluation mode No. 2)
	Progression	No Progression	Total
Progression*	15	2	17
No Progression**	7	166	173
Total	22	168	190

Clinical Sensitivity: 68.2% (15/22) (95% Cl: 48.7% to 87.6%) Clinical Specificity: 98.8% (166/168) (95% Cl: 97.2% to 100.0%)

* Progression (PD - Progressive Disease):

from CR: any detectable M-protein OR abnormal FLC ratio (involved FLC must be at least doubling from normal range),
from PR or VGPR: 50% increase in serum M-protein to > 5 g/L OR 50% increase in urine Mprotein to > 200 mg/day (a visible peak must be present); OR involved FLC increase greater than 50% to 100 mg/L at any time.

** No Progression: all other cases.

b) Stability

Shelf-life studies were conducted using the FLC Kappa and FLC Lambda kits and FLC controls Level 1 and Level 2. All results met stability acceptance criteria and product stability claims as listed in the tables below:

Stability of Kit (FLC Kappa and FLC Lambda)

Kit	Shelf Life
FLC Kappa	12 months at 2 - 8 °C
FLC Lambda	12 months at 2 - 8 °C

12

Stability of Controls (FLC Control Level 1 and FLC Control Level 2)

Kit	Shelf Life
	Claimed Shelf Life	Real time stability (time point available)	Claimed Stability
FLC Control Level 1	4 years at 2 - 8 °C	3 years at 2 - 8 °C	2 years at 2 - 8 °C
FLC Control Level 2	3 years at 2 - 8 °C	3 years at 2 - 8 °C	2 years at 2 - 8 °C

6. CONCLUSION

The submitted information in this premarket notification is complete and supports a substantial equivalence decision.