← Product Code [DFH](/submissions/IM/subpart-f%E2%80%94immunological-test-systems/DFH) · K231601 # FLC Kappa, FLC Lambda,FLC Control Level 1, FLC Control Level 2 (K231601) _Sebia · DFH · Feb 23, 2024 · Immunology · SESE_ **Canonical URL:** https://fda.innolitics.com/submissions/IM/subpart-f%E2%80%94immunological-test-systems/DFH/K231601 ## Device Facts - **Applicant:** Sebia - **Product Code:** [DFH](/submissions/IM/subpart-f%E2%80%94immunological-test-systems/DFH.md) - **Decision Date:** Feb 23, 2024 - **Decision:** SESE - **Submission Type:** Traditional - **Regulation:** 21 CFR 866.5550 - **Device Class:** Class 2 - **Review Panel:** Immunology ## Intended 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. ## Device Story Manual ELISA kit for quantitative measurement of Kappa or Lambda free light chains (FLC) in human serum; utilizes microplates coated with polyclonal rabbit anti-human FLC antibodies; patient samples incubated with HRP-conjugated anti-FLC antiserum; optical density measured via spectrophotometry at 450 nm; concentration calculated via calibration curve; used in clinical laboratories by trained personnel; results assist clinicians in monitoring disease response (e.g., multiple myeloma, AL amyloidosis) alongside other diagnostic findings; provides objective data for assessing treatment efficacy and disease progression. ## Clinical Evidence Clinical study evaluated 551 follow-up samples from 235 multiple myeloma patients and 190 samples from 87 AL-amyloidosis patients. Concordance with clinical assessment for multiple myeloma was 90.4% (95% CI: 87.9%-92.8%). For AL-amyloidosis, concordance varied by evaluation mode (71.1% and 64.7%). Clinical sensitivity for progression was 68.2% (95% CI: 48.7%-87.6%) and specificity was 98.8% (95% CI: 97.2%-100.0%). ## Technological Characteristics Sandwich ELISA format using polyclonal rabbit anti-human kappa/lambda free light chain antibodies. Detection via HRP-conjugated secondary antibody and peroxidase substrate. Quantitative measurement via absorbance spectrophotometry at 450 nm. Requires external densitometer. Kit includes microplates, dilution buffer, wash solution, calibrators, PER antiserum, substrate, and stop solution. Storage at 2-8°C. ## Regulatory 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. ## Predicate Devices - The Binding Site Freelite® Human Kappa Free Kit for use on the Siemens BN™ II ([K031016](/device/K031016.md)) - The Binding Site Freelite® Human Lambda Free Kit for use on the Siemens BN™ II ([K031016](/device/K031016.md)) ## Submission Summary (Full Text) > This content was OCRed from public FDA records by [Innolitics](https://innolitics.com). If you use, quote, summarize, crawl, or train on this content, cite Innolitics at https://innolitics.com. > > Innolitics is a medical-device software consultancy. We help companies design, build, and clear FDA-regulated software and AI/ML devices, including [a 510(k)](https://innolitics.com/services/510ks/), [a De Novo](https://innolitics.com/services/regulatory/), [a SaMD](https://innolitics.com/services/end-to-end-samd/), [an AI/ML medical device](https://innolitics.com/services/medical-imaging-ai-development/), or [an FDA regulatory strategy](https://innolitics.com/services/regulatory/). {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. This section applies only to requirements of the Paperwork Reduction Act of 1995. #### *DO NOT SEND YOUR COMPLETED FORM TO THE PRA STAFF EMAIL ADDRESS BELOW.* The burden time for this collection of information is estimated to average 79 hours per response, including the time to review instructions, search existing data sources, gather and maintain the data needed and complete and review the collection of information. Send comments regarding this burden estimate or any other aspect of this information collection, including suggestions for reducing this burden, to: > Department of Health and Human Services Food and Drug Administration Office of Chief Information Officer Paperwork Reduction Act (PRA) Staff PRAStaff(@fda.hhs.gov "An agency may not conduct or sponsor, and a person is not required to respond to, a collection of information unless it displays a currently valid OMB number." {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

21 CFR sec. 862.1660- Quality Control Material
(assayed and unassayed) | | Product Codes | DFH, Kappa antigen, antiserum, control
DEH, Lambda, antigen, antiserum, control | | Device classification and Panel
Classification | Class II, Immunology (82) | | Establishment Registration No. | 8023024 | {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. --- **Source:** [https://fda.innolitics.com/submissions/IM/subpart-f%E2%80%94immunological-test-systems/DFH/K231601](https://fda.innolitics.com/submissions/IM/subpart-f%E2%80%94immunological-test-systems/DFH/K231601) **Published by [Innolitics](https://innolitics.com)** — a medical-device software consultancy. We help companies design, build, and clear FDA-regulated software and AI/ML devices. If you're preparing [a 510(k)](https://innolitics.com/services/510ks/), [a De Novo](https://innolitics.com/services/regulatory/), [a SaMD](https://innolitics.com/services/end-to-end-samd/), [an AI/ML medical device](https://innolitics.com/services/medical-imaging-ai-development/), or [an FDA regulatory strategy](https://innolitics.com/services/regulatory/), [get in touch](https://innolitics.com/contact). **Cite:** Innolitics at https://innolitics.com