In-vitro diagnostic reagents for the quantitative determination of free light chains (FLC), type kappa or type lambda in human serum and EDTA-plasma. FLC measurements are used as an aid in the diagnosis and monitoring of multiple myeloma (MM) and as an aid in the diagnosis of amyloidosis (AL) in conjunction with other laboratory and clinical findings.

The response category assignment of 'Complete Response' for the monitoring of MM, is reliant upon the combination of clinical history and other tests including protein electrophoresis, immunofixation and bone marrow, imaging and urine assessments.

Device Description

The N Latex FLC (free light chain) assays are in vitro diagnostic reagents for the quantitative determination of free light chains, type kappa or type lambda, in human serum and EDTA plasma by means of particle-enhanced immunoassay determination. Used in conjunction with other clinical and laboratory findings, FLC measurements are used as an aid in the diagnosis and monitoring of multiple myeloma (MM) and as an aid in the diagnosis of amyloidosis (AL).

Polystyrene particles coated with antibodies to human free light chains, type kappa or lambda, respectively, are agglutinated with samples containing FLC. A concentration curve is obtained by monitoring agglutination and measuring the increase in turbidity. The actual change in absorbance is proportional to the concentration of the respective protein in the sample. The result is evaluated by comparison with a standard of known concentration.

AI/ML Overview

The provided text describes the submission for a 510(k) premarket notification for the N Latex FLC kappa and N Latex FLC lambda assays, adapted for use on the Atellica® CH Analyzer. The submission aims to demonstrate substantial equivalence to previously cleared devices.

Here's a breakdown of the requested information based on the provided text:

1. A table of acceptance criteria and the reported device performance

The document states that "The test methods and acceptance criteria used for N Latex FLC kappa and lambda on the Atellica® CH Analyzer are equivalent to those used for the predicate device." However, specific numerical acceptance criteria and reported device performance (e.g., accuracy, precision, sensitivity, specificity values) are not detailed in the provided text. The text mentions "comparative testing was performed, and the results obtained demonstrate substantial equivalent performance," but does not present the direct results of these tests against specific acceptance criteria.

The only comparative performance aspect mentioned specifically is the "Analytical Measuring Range":

Feature	Predicate (BN Systems)	Modified Device (Atellica® CH Analyzer)
Analytical Measuring Range
Kappa	Typical range: 3.4 to 110 mg/L	3.91 to 60 mg/L
Lambda	Typical range: 1.9 to 60 mg/L	5.47 to 70 mg/L

Note: Without the specific performance study results (e.g., accuracy, precision, limit of detection, linearity) and their corresponding acceptance criteria, a complete table cannot be generated from the given text.

2. Sample size used for the test set and the data provenance (e.g. country of origin of the data, retrospective or prospective)

The text mentions "comparative testing" and "verification activities" but does not specify the sample size used for these test sets.
Data provenance (country of origin, retrospective/prospective) is also not specified.

3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts (e.g. radiologist with 10 years of experience)

This product is an in-vitro diagnostic reagent for quantitative determination, not an imaging device requiring expert interpretation for ground truth. The "ground truth" for such devices typically relies on reference methods or spiked samples with known concentrations. The text does not mention the involvement of experts or their qualifications for establishing ground truth, as it's not applicable in the same way it would be for an image-based diagnostic.

4. Adjudication method (e.g. 2+1, 3+1, none) for the test set

Adjudication methods like 2+1 or 3+1 are typically used in studies involving human interpretation (e.g., radiologists reading images). For an in-vitro diagnostic device that provides quantitative results, an adjudication method in this sense is not applicable and therefore not mentioned.

5. If a multi-reader multi-case (MRMC) comparative effectiveness study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance

There is no mention of a multi-reader multi-case (MRMC) comparative effectiveness study. This type of study is specifically relevant for imaging devices or AI-assisted diagnostic tools that involve human readers. The N Latex FLC assays are IVD reagents that provide quantitative measurements, meaning human "readers" don't interact with the device in the same way they would with an imaging AI. The submission focuses on the performance of the assay on a new instrument platform.

6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done

The N Latex FLC assays are standalone in the sense that they provide a quantitative result without human "interpretation" of the analytical output in the way an imaging AI would be interpreted. It's a fully automated analytical process on the Atellica® CH Analyzer. The entire study implicitly focuses on the standalone analytical performance of the combined reagent/analyzer system. The results generated by the device are numerical values, which are then used by clinicians in conjunction with other findings.

7. The type of ground truth used (expert consensus, pathology, outcomes data, etc)

The text does not explicitly state the type of ground truth used. For quantitative laboratory assays, ground truth is typically established through:

Reference methods: Comparing results to a well-established, often more complex or gold-standard analytical method.
Certified reference materials: Using samples with accurately known concentrations of the analyte.
Commutability studies: Ensuring that control materials behave similarly to patient samples.

The document mentions "Traceability: Internal Reference Plasma Pool," which suggests that internal standards are used to calibrate and ensure consistency, contributing to the establishment of reliable measurements which act as the 'ground truth' for the assay's performance claims.

8. The sample size for the training set

The provided text describes a 510(k) submission for an in-vitro diagnostic reagent system, not an AI/ML algorithm. Therefore, the concept of a "training set" in the context of machine learning does not apply. The assays are based on established immunoassay principles, not on learned patterns from a training dataset.

9. How the ground truth for the training set was established

As explained in point 8, the concept of a "training set" for an AI/ML algorithm is not applicable here.

Summary

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May 3, 2019

Siemens Healthcare Diagnostics Products GmbH Christine Perkins Regulatory Specialist Emil-von-Behring Str-76 35041 Marburg, Germany

Re: K190879

Trade/Device Name: N Latex FLC kappa. N Latex 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: April 3, 2019 Received: April 4, 2019

Dear Christine Perkins:

We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food, Drug, and Cosmetic Act (Act) that do not require approval of a premarket approval application (PMA). You may, therefore, market the device, subject to the general controls provisions of the Act. Although this letter refers to your product as a device, please be aware that some cleared products may instead be combination products. The 510(k) Premarket Notification Database located at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/pmn.cfm identifies combination product submissions. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.

If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. In addition, FDA may publish further announcements concerning your device in the Federal Register.

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

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801 and Part 809); medical device reporting of medical device-related adverse events) (21 CFR 803) for devices or postmarketing safety reporting (21 CFR 4, Subpart B) for combination products (see https://www.fda.gov/CombinationProducts/GuidanceRegulatoryInformation/ucm597488.htm); good manufacturing practice requirements as set forth in the quality systems (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 http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm.

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/DeviceRegulationandGuidance/) and CDRH Learn (http://www.fda.gov/Training/CDRHLearn). Additionally, you may contact the Division of Industry and Consumer Education (DICE) to ask a question about a specific regulatory topic. See the DICE website (http://www.fda.gov/DICE) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).

Sincerely,

Doug Jeffery Acting Deputy Director Division of Immunology and Hematology Devices OHT7: Office of In Vitro Diagnostics and Radiological Health Office of Product Evaluation and Quality Center for Devices and Radiological Health

Enclosure

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Indications for Use

510(k) Number (if known) K190879

Device Name N Latex FLC kappa N Latex FLC lambda

Indications for Use (Describe)

X Prescription Use (Part 21 CFR 801 Subpart D)

| Over-The-Counter Use (21 CFR 801 Subpart C)

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510(k) Summary per 21 CFR 807.92 Type of 510(k): Special 510(k)

This 510(k) Summary of Safety and Effectiveness is being submitted in accordance with the requirements of the Safe Medical Device Act of 1990 and 21 CFR 807.92.

The assigned 510(k) number is: _______K190879

1. Submitter

Siemens Healthcare Diagnostics Products GmbH Emil-von-Behring-Str. 76 35041 Marburg, Germany

Contact Person :	Christine Perkins
Email :	christine.perkins@siemens-healthineers.com
Phone:	302-631-8811
Fax:	302-631-6299
Date of Preparation:	April 03, 2019

2. Device Information

Proprietary Name:	N Latex FLC kappa assayN Latex FLC lambda assay
Common or Usual Name:	Light Chain immunological test system
Product Code :	DFH (kappa)DEH (lambda)
Classification Name:	Immunoglobulin (light chain specific)immunological test system per 21CFR866.5550
Regulatory Class:	II
510(k) Review Panel:	Clinical Immunology (82)

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3. Legally Marketed Unmodified / Predicate Devices

Cleared for use on Siemens' BN Systems under K171742 on November 17, 2017 as an aid in the diagnosis of multiple myeloma (MM) and amyloidosis; cleared under K182098 on November 1, 2018 for monitoring of MM:

Trade Name	Common/UsualName	Classification	ProductCode	Panel	FDAclearance
N LatexFLC kappa	Immunoglobulin(light chain specific)immunological testsystem	Class II per21CFR866.5550	DFH	Immunology(82)	K171742 K182098
N LatexFLC lambda	Immunoglobulin(light chain specific)immunological testsystem	Class II per21CFR866.5550	DEH	Immunology(82)	K171742 K182098

4. Device Description / Test Principle of the Modified Device

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5. Intended Use / Indications for Use

N Latex FLC kappa and N Latex FLC lambda assays

The response category assignment of 'Complete Response' for the monitoring of MM. is reliant upon the combination of clinical history and other tests including protein electrophoresis, immunofixation and bone marrow, imaging and urine assessments.

N FLC Supplementary Reagent

Supplementary reagent for the immunonephelometric determination of free light chains (FLC), type kappa and type lambda on BN Systems.

Supplementary reagent for the turbidimetric determination of free light chains (FLC), type kappa and type lambda on the Atellica® CH Analyzer.

A mixture of both supplementary reagents is used to suppress interference by rheumatoid factors and human anti-mouse antibodies (HAMA).

6. Special Conditions for Use Statements

For prescription use only.

The result of the FLC kappa or 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 FLC kappa or FLC lambda 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 and FLC lambda levels is changed, additional sequential testing should be carried out. Prior to changing assays, the laboratory MUST confirm baseline values for patients being serially monitored.

7. Special instrument requirements:

Atellica® CH Analyzer (K151767) BN II System (K943997) BN ProSpec® (K001647)

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8. Technological characteristics

Similarities and Differences to the predicate:

A comparison of the similarities and differences between the proposed Atellica® CH N Latex FLC assays versus the BN Systems' N Latex FLC assays (predicates):

PredicateSiemens HealthcareBN SystemsN Latex FLC kappaN Latex FLC lambda(K171742, K182098)		Siemens HealthcareAtellica® CH AnalyzerModified DevicesN Latex FLC kappaN Latex FLC lambda
Indications for Use	In-vitro diagnostic reagents for thequantitative determination of free lightchains (FLC), type kappa or type lambdain human serum and EDTA-plasma bymeans of particle-enhancedimmunonephelometry using the BNSystems. FLC measurements are usedas an aid in the diagnosis andmonitoring of multiple myeloma (MM)and as an aid in the diagnosis ofamyloidosis (AL) in conjunction withother laboratory and clinical findings.The response category assignment of'Complete Response' for the monitoringof MM, is reliant upon the combination ofclinical history and other tests includingprotein electrophoresis, immunofixationand bone marrow, imaging and urineassessments.	In-vitro diagnostic reagents for thequantitative determination of freelight chains (FLC), type kappa ortype lambda in human serum andEDTA-plasma. FLC measurementsare used as an aid in the diagnosisand monitoring of multiple myeloma(MM) and as an aid in the diagnosisof amyloidosis (AL) in conjunctionwith other laboratory and clinicalfindings.Same
Sample Type	Human serum and EDTA plasma	Same
ReagentPackaging	3 x 1 mL	Same
ReagentHandling	Bottles placed directly on system	Reagents poured into reagentcontainers
Units	mg/L	Same
DetectionMethod	Nephelometry	Turbidimetry
Measurement	Quantitative	Same
DetectionAntibody	Monoclonal mouse anti-human FLCkappaMonoclonal mouse anti-antibody FLClambda	Same
ReagentComposition	Polystyrene particles coated withmonoclonal antibodies	Same
Traceability	Internal Reference Plasma Pool	Same
	PredicateSiemens HealthcareBN SystemsN Latex FLC kappaN Latex FLC lambda(K171742, K182098)	Siemens HealthcareAtellica® CH AnalyzerModified DevicesN Latex FLC kappaN Latex FLC lambda
Calibrators	One level	Same
CalibrationInterval	42 days	Same
AnalyticalMeasuringRange	Typical range:kappa: 3.4 to 110 mg/Llambda: 1.9 to 60 mg/L	kappa: 3.91 to 60 mg/Llambda: 5.47 to 70 mg/L
ReferenceInterval	kappa: 8.24 to 28.90 mg/Llambda: 9.10 to 32.60 mg/LRatio: 0.53 to 1.51	Same

Comparison of Technological Characteristics

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The modification of the predicate devices is to add the Atellica® CH Analyzer to the N Latex FLC kappa and lambda assays.

7. Summary of Design Control Activities

A risk analysis was performed with risks identified. Mitigation of risk to acceptable levels was achieved through verification activities summarized below.

7.1 Risk Analysis

Risk analysis was performed according to the ISO14971:2007 standard, Medical Devices - Application of Risk Management to Medical Devices. The change to the N Latex FLC kappa and N Latex FLC lambda assays, previously cleared for use on the BN Systems, is to adapt them for use on the Atellica® CH Analyzer. The reagents used for both systems are identical in composition, packaging and labeling.

Each difference was analyzed, and its effect identified. Severity and probability were estimated by risk class. Risks were mitigated to the degree acceptable.

7.2. Verification Activities

Based on the results of the risk analysis, verification activities were identified, pertinent studies were determined and acceptance criteria established.

The test methods and acceptance criteria used for N Latex FLC kappa and lambda on the Atellica® CH Analyzer are equivalent to those used for the predicate device.

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8. Comments on Substantial Equivalency

The reagents for the proposed devices and the cleared devices are identical in composition, labeling and packaging. Comparative testing was performed, and the results obtained demonstrate substantial equivalent performance.

The use of these reagents on another instrument platform with a different measuring technology, i.e., nephelometry versus turbidimetry, does not affect safety and efficacy when used according to the product labeling.

9. Conclusion

The modified devices, N Latex FLC kappa and lambda on the Atellica® CH Analyzer, are substantially equivalent to the predicate devices based on intended use design, and basic scientific principle and performance.

Results from the risk analysis and design control activities with comparative testing support a substantial equivalence decision.

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).