The Kappa light chains assay is an in vitro diagnostic test used for the quantitative determination of immunoglobulin bound and free kappa light chains (KAPPA) in serum and in Li-heparin plasma by immunoturbidimetry on Synchron LX20 System. Measurement of type 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, in conjunction with other clinical and laboratory findings.

Device Description

The Kappa light chains assay is an in vitro diagnostic test used for the quantitative determination of immunoglobulin bound and free kappa light chains (KAPPA) in serum and in Li-heparin plasma by immunoturbidimetry on Synchron LX20 System. The determination of Kappa light chains is based on the specific turbidimetric reaction, which occurs between a polyclonal antiserum against human Immunoglobulin Kappa light chains and its corresponding antigen under optimal pH conditions and in the presence of polyethylene glycol (PEG). The turbidity of the immune complex is proportional to the concentration of the analyte in the sample.

AI/ML Overview

Here's an analysis of the provided text regarding the acceptance criteria and the study that proves the device meets those criteria:

Device: Kappa light chains assay (Sentinel)

Predicate Device: Beckman IMMAGE Immunochemistry System Kappa light chain (K964260)

1. Table of Acceptance Criteria and Reported Device Performance

The submission focuses on establishing substantial equivalence to a predicate device, primarily through performance similarities rather than explicit, pre-defined quantitative acceptance criteria with thresholds for accuracy, sensitivity, or specificity against a clinical ground truth. The acceptance is implied by acceptable correlation and precision compared to its own internal metrics and the overall 'similar performance characteristics' to the predicate.

Performance Metric	Acceptance Criteria (Implied)	Reported Device Performance
Method Comparison (Correlation with Predicate)	"Acceptable correlation" with Beckman Kappa light chain (K964260) on IMMAGE nephelometer Analyzer.	Correlation coefficient (r): 0.985
	Slope (implied close to 1)	Slope: 0.900
	Y-intercept (implied close to 0)	Y-intercept: 134 mg/dL
Precision (Total Imprecision)	"Acceptable" %CV values.	Ranges from 2.4% to 6.8% CV across 6 levels.
Precision (Between Days)	"Acceptable" %CV values.	Ranges from 1.7% to 5.5% CV across 6 levels.
Precision (Repeatability)	"Acceptable" %CV values.	Ranges from 1.5% to 4.1% CV across 6 levels.
Analytical Measurement Range (AMR) - Lower Limit	Not explicitly stated but expected to be within a clinically relevant range.	Found lower limit: 31.2 mg/dL. Claimed: 35 mg/dL.
Analytical Measurement Range (AMR) - Upper Limit	Not explicitly stated but expected to be within a clinically relevant range.	Found upper limit: 750.13 mg/dL. Claimed: 750 mg/dL.

2. Sample Size Used for the Test Set and Data Provenance

Method Comparison: The document states "Comparative performance studies were conducted," but does not explicitly mention the sample size of patient samples used for the method comparison study. It does mention that the Kappa light chains assay on Synchron LX20 System was compared using "calibrator material with assigned Kappa Light chains concentration based on definition of Kappa Light chains as Whole IgG content (MW 150000)." This suggests that at least part of the comparison involved characterized calibrator samples rather than solely patient samples.
Precision Studies: Two levels for 20x2x2 test (day x run x rep) on 6 levels implies:
- 20 days x 2 runs/day x 2 replicates/run = 80 measurements for each of the 6 levels.
- Total tests for precision: 6 levels * 80 tests/level = 480 tests.
AMR Studies: Not explicitly stated.
Data Provenance: The document does not specify the country of origin of the data or whether the studies were retrospective or prospective.

3. Number of Experts Used to Establish the Ground Truth for the Test Set and Their Qualifications

This type of in-vitro diagnostic (IVD) device (quantitative biochemical assay) does not typically rely on "experts" to establish ground truth in the same way an imaging or pathology device might. The "ground truth" for method comparison is the measurement obtained by the predicate device (Beckman IMMAGE Immunochemistry System Kappa light chain), which is itself a quantitative assay.

4. Adjudication Method for the Test Set

Not applicable. This is a comparison of quantitative measurements between two instruments/assays, not an interpretation that requires adjudication (like reading medical images).

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done, and Its Effect Size

No, a Multi-Reader Multi-Case (MRMC) comparative effectiveness study was not done. This type of study is relevant for devices where human readers interpret outputs (e.g., medical images), and the AI either assists or replaces human interpretation. This device is a quantitative diagnostic assay.

6. If a Standalone (Algorithm Only Without Human-in-the-Loop Performance) Was Done

Yes, the studies presented (method comparison, precision, AMR) are all standalone performance evaluations of the device (Kappa light chains assay on Synchron LX20 System). There is no "human-in-the-loop" component described for its operation or result generation; it's an automated in vitro diagnostic test system.

7. The Type of Ground Truth Used

The primary "ground truth" for the method comparison study was the measurements obtained from the predicate device (Beckman IMMAGE Immunochemistry System Kappa light chain, K964260). For precision and AMR, the ground truth refers to the intrinsic analytical performance characteristics of the new device itself, often evaluated against known concentrations or through repeated measurements, rather than an external clinical "ground truth" (e.g., pathology or outcomes data). The assays are also traceable to ERM-DA 470 (European Reference Material) from BCR (EG Community Bureau of Reference), corresponding to RPPHS (Reference Preparation for Protein in Human Serum), which serves as a metrological ground truth for standardization.

8. The Sample Size for the Training Set

The document does not specify a separate training set. For IVD submissions like this, the development process for an assay involves calibration and optimization, but typically, the pre-market submission focuses on the validation or test data for the final, locked-down assay. If there was an implicit "training" or development phase, the data used for that is not explicitly detailed as a distinct 'training set' in the context of machine learning.

9. How the Ground Truth for the Training Set Was Established

As no explicit "training set" is mentioned in the context of machine learning, this question isn't directly applicable. The assay's development (which could be considered analogous to training) would involve establishing appropriate calibration curves and reagent formulations based on known standards and reference materials (e.g., ERM-DA 470).

Summary

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K083602

SFP = 3 2009

Page 2 of 5

510(k) Summary

Submitter's Name/Address SENTINEL CH. Via Robert Koch, 2 20152 Milan - Italv

Date of Preparation of this Summarv: Device Trade or Proprietary Name:

Classification Name:

Classification Number/Class: Product Code:

Contact Person Fabio Rota Technical Director +39 02 3455148 Fax: +39 02 34551464

July 10th , 2009 Kappa light chains Assay Immunoglobulin (light chain specific) immunological test system. Class II / 866.5550 DFH

This summary of 510(k) safety and effectiveness information is being submitted in accordance with the requirements of SMDA 1990 and 21 CFR 807.92.

The assigned 510(k) number is: K083602

Test Description:

The determination of Kappa light chains is based on the specific turbidimetric reaction, which occurs between a polyclonal antiserum against human Immunoglobulin Kappa light chains and its corresponding antigen under optimal pH conditions and in the presence of polyethylene glycol (PEG). The turbidity of the immune complex is proportional to the concentration of the analyte in the sample.

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Substantial Equivalence:

The Kappa light chains assay is substantially equivalent to Beckman IMMAGE Immunochemistry System Kappa light chain (K964260) on the 1MMAGE nephelometer Analyzer. Both assays yield similar Performance Characteristics.

Similarities:

Both assays are used for the quantitative determination of Kappa light chains (free and bound).
Both assays are based on immunologic reaction between the Kappa light chains of human immunoglobulin and a specific polyclonal.
Both assay detect bound and free Kappa light chains
Both assays utilize reagents in R1 and R2 format.
Both assays are traceable to ERM-DA 470 (European Reference Material) from BCR (EG Community Bureau of Reference), corresponding to RPPHS (Reference Preparation for Protein in Human Serum).
Both assays yield similar clinical results.

Differences:

The predicate device assay uses serum only as specimens. Sentinel assay uses serum and Li- heparin plasma.
The predicate device quantificates Kappa light chains by nephelometry. Sentinel assay quantificates Kappa light chains by immunoturbidimetry.
In the predicate device, Kappa values are given in mg/dL and expressed as "equivalent weight of the intact immunoglobulin molecules (IgG + IgA + IgM = Kappa + Lambda). Thus the Molecular Weight of the Light chains is considered to be 150000 dalton (as the MW of whole IgG).
- In the Sentinel assay, Kappa values are given in mg/dL and expressed as content of Immunoglobulin light chains. The Molecular Weight of the Light chains is estimated to be 25000 dalton. Therefore, the results on Beckman Immage are about 3 times higher than results on Synchron LX.

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Intended Use:

The Kappa light chains assay is an in vitro diagnostic test used for the quantitative determination of immunoglobulin bound and free kappa light chains (KAPPA) in serum and in Li-heparin plasma by immunoturbidimetry on Synchron LX20 System. Measurement of type 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 theumatoid arthritis or systemic lupus erythematosus, in conjunction with other clinical and laboratory findings.

Performance Characteristics:

Comparative performance studies were conducted using the Synchron LX20 System. Sentinel Kappa light chains on Synchron LX20 System method comparison vielded acceptable correlation with the Beckman Kappa light chain (K964260) on IMMAGE nephelometer Analyzer.

Method comparison

Kappa light chains assay on Synchron LX20 System was calibrator material with assigned Kappa Light chains concentration based on definition of Kappa Light chains as Whole IgG content (MW 150000).

This comparison showed a correlation coefficient (r) of 0.985, slope of 0.900 and Y-intercept of 134 mg/dL.

Conclusion - Data generated demonstrated an acceptable correlation between the Kappa Light chains assay on the Synchron LX20 System vs. the IMMAGE Immunochemistry System Kappa light chains (K964260) on IMMAGE nephelometer Analyzer.

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Precision:

Mean(mg/dL)	Total Imprecision		Between days		Repeatability(Repeatibility)
	SD(mg/dL)	CV%	SD(mg/dL)	CV%	SD(mg/dL)	CV%
125.7	8.55	6.8	6.88	5.5	5.08	4.1
476.9	14.54	3.0	12.34	2.6	7.7	1.6
93.5	5.63	6.0	3.33	3.6	3.44	3.7
104.4	4.46	4.3	3.74	3.6	1.55	1.5
651.9	25.27	3.9	22.40	3.4	11.69	1.8
695.0	16.76	2.4	11.59	1.7	12.11	1.7

Precision studies were conducted using Kappa light chains on the Synchron LX20 System. The found %CV values for 20x2x2 test (day x run x rep) on 6 levels (N=80 for each level) were:

Analytical Measurement Range (AMR):

The found lower limit of the AMR of Lambda light chains on the Synchron LX20 System was 31.2 mg/dL. The found upper limit of the AMR was 750.13 mg/dL.

The claimed AMR will be 35 to 750 mg/dL.

Conclusion for 510(k) Summary:

These method comparison, precision and AMR data demonstrate that the analytical performance of the Kappa light chains on the Synchron LX20 System is substantially equivalent to IMMAGE Immunochemistry System Kappa light chain (K964260) on the IMMAGE nephelometer Analyzer.

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Image /page/4/Picture/0 description: The image shows the logo for the Department of Health & Human Services (HHS). The logo features a stylized image of an eagle with its wings spread, symbolizing protection and care. The text "DEPARTMENT OF HEALTH & HUMAN SERVICES • USA" is arranged in a circular pattern around the eagle, indicating the department's name and national affiliation. The logo is simple, using black lines on a white background.

Food and Drug Administration 10903 New Hampshire Avenue Document Mail Center - WO66-0609 Silver Spring, MD 20993-0002

SENTINEL CH SpA c/o Dr. Yangtse Portelles Regulatory Affairs Via Robert Koch, 2 20152 Milan Italy

SEP - 8 2009

Re: K083602

Trade/Device Name: Kappa Light Chains Assay Regulation Number: 21 CFR §866.5550 Regulation Name: Immunoglobulin (light chain specific) immunological test system Regulatory Class: Class II Product Code: DFH Dated: August 26, 2009 Received: August 31, 2009

Dear Dr. Portelles:

We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food, Drug, and Cosmetic Act (Act) that do not require approval of a premarket approval application (PMA). You may, therefore, market the device, subject to the general controls provisions of the Act. The general controls provisions of the Act include requirements for annual registration. Iisting of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration.

If your device is classified (see above) into class II (Special Controls), it may be subject to such additional controls. Existing major regulations affecting your device can be found in Title 21, Code of Federal Regulations (CFR), Parts 800 to 895. In addition, FDA may publish further announcements concerning your device in the Federal Register.

Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Part 801); medical device reporting (reporting of medical device-related adverse events) (21 CFR 803); good manufacturing practice requirements as set

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Page 2 - Dr. Yangtse Portelles

forth in the quality systems (QS) regulation (21 CFR Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

If you desire specific advice for your device on our labeling regulation (21 CFR Part 801), please go to http://www.fda.gov/AboutFDA/CentersOffices/CDRH/CDRHOffices/ucm115809.htm for the Center for Devices and Radiological Health's (CDRH's) Office of Compliance. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to

http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm for the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance.

You may obtain other general information on your responsibilities under the Act from the Division of Small Manufacturers, International and Consumer Assistance at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address http://www.fda.gov/MedicalDevices/Resourcesfor You/Industry/default.htm.

Sincerely yours,

ia m chan

Maria M. Chan. Ph.D. Director Division of Immunology and Hematology Devices Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health

Enclosure

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Indications for Use

510(k) Number (if known): K083602

Device Name: Kappa light chains

Indications for Use:

Prescription Use X AND/OR (Part 21 CFR 801 Subpart D)

Over-The-Counter Use_ (21 CFR 801 Subpart C)

(PLEASE DO NOT WRITE BELOW THIS LINE - CONTINUE ON ANOTHER PAGE IF NEEDED)

Concurrence of CDRH, Office of In Vitro Diagnostics Devices (OIVD)

Mana mchan

Division Sign-t

Office of In Vitro Diagnostic Device Evaluation and Safety

51000 KO 85602

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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).