N Latex FLC kappa, N Latex FLC lambda

K190879 · Siemens Healthcare Diagnostics Products GmbH · DFH · May 3, 2019 · Immunology

Device Facts

• Record ID: K190879
• Device Name: N Latex FLC kappa, N Latex FLC lambda
• Applicant: Siemens Healthcare Diagnostics Products GmbH
• Product Code: DFH · Immunology
• Decision Date: May 3, 2019
• Decision: SESE
• Submission Type: Special
• Regulation: 21 CFR 866.5550
• Device Class: Class 2

Intended Use

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 Story

N Latex FLC assays are in-vitro diagnostic reagents for quantitative determination of free light chains (FLC) in human serum and EDTA-plasma. Input samples are processed via particle-enhanced immunoassay on Atellica CH or BN systems. Polystyrene particles coated with monoclonal antibodies agglutinate with FLC in samples; agglutination increases turbidity/light scattering. Device measures change in absorbance (turbidimetry) or light scattering (nephelometry) proportional to protein concentration. Results are compared against known standards to quantify FLC levels. Used in clinical laboratories by trained personnel. Output assists physicians in diagnosing and monitoring multiple myeloma and amyloidosis. Clinical utility relies on integration with patient history, protein electrophoresis, immunofixation, bone marrow, imaging, and urine assessments. Supplementary reagents suppress interference from rheumatoid factors and HAMA.

Clinical Evidence

Bench testing only. Verification and validation activities performed per design control requirements to confirm performance on the Atellica CH Analyzer platform.

Technological Characteristics

Particle-enhanced immunoassay using polystyrene particles coated with monoclonal mouse anti-human FLC antibodies. Detection via turbidimetry (Atellica CH) or nephelometry (BN Systems). Quantitative measurement in mg/L. Reagents include supplementary mixture to suppress rheumatoid factor and HAMA interference. Calibration interval 42 days.

Indications for Use

Indicated for the quantitative determination of free light chains (kappa and lambda) in human serum or plasma on the Atellica CH Analyzer.

Regulatory Classification

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

• N Latex FLC kappa (K182098)
• N Latex FLC lambda (K182098)

Submission Summary (Full Text)

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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 ([e-mail]) or phone [phone] 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)

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.

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 : | [e-mail] |
| Phone: | 302-631-8811 |
| Fax: | 302-631-6299 |
| Date of Preparation: | April 03, 2019 |

### 2. Device Information

| Proprietary Name: | N Latex FLC kappa assay<br>N Latex FLC lambda assay |
|-----------------------|------------------------------------------------------------------------------------------|
| Common or Usual Name: | Light Chain immunological test system |
| Product Code : | DFH (kappa)<br>DEH (lambda) |
| Classification Name: | Immunoglobulin (light chain specific)<br>immunological test system per 21CFR<br>866.5550 |
| 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/Usual<br>Name | Classification | Product<br>Code | Panel | FDA<br>clearance |
|-----------------------|--------------------------------------------------------------------------|-----------------------------------|-----------------|--------------------|--------------------|
| N Latex<br>FLC kappa | Immunoglobulin<br>(light chain specific)<br>immunological test<br>system | Class II per<br>21CFR<br>866.5550 | DFH | Immunology<br>(82) | K171742<br>K182098 |
| N Latex<br>FLC lambda | Immunoglobulin<br>(light chain specific)<br>immunological test<br>system | Class II per<br>21CFR<br>866.5550 | DEH | Immunology<br>(82) | K171742<br>K182098 |

## 4. Device Description / Test Principle of the Modified Device

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.

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## 5. Intended Use / Indications for Use

### N Latex FLC kappa and N Latex FLC lambda assays

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.

### 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):

| Predicate<br>Siemens Healthcare<br>BN Systems<br>N Latex FLC kappa<br>N Latex FLC lambda<br>(K171742, K182098) | | Siemens Healthcare<br>Atellica® CH Analyzer<br>Modified Devices<br>N Latex FLC kappa<br>N Latex FLC lambda |
|----------------------------------------------------------------------------------------------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Indications for Use | In-vitro diagnostic reagents for the<br>quantitative determination of free light<br>chains (FLC), type kappa or type lambda<br>in human serum and EDTA-plasma by<br>means of particle-enhanced<br>immunonephelometry using the BN<br>Systems. FLC measurements are used<br>as an aid in the diagnosis and<br>monitoring of multiple myeloma (MM)<br>and as an aid in the diagnosis of<br>amyloidosis (AL) in conjunction with<br>other laboratory and clinical findings.<br><br>The response category assignment of<br>'Complete Response' for the monitoring<br>of MM, is reliant upon the combination of<br>clinical history and other tests including<br>protein electrophoresis, immunofixation<br>and bone marrow, imaging and urine<br>assessments. | In-vitro diagnostic reagents for the<br>quantitative determination of free<br>light chains (FLC), type kappa or<br>type lambda in human serum and<br>EDTA-plasma. FLC measurements<br>are used as an aid in the diagnosis<br>and monitoring of multiple myeloma<br>(MM) and as an aid in the diagnosis<br>of amyloidosis (AL) in conjunction<br>with other laboratory and clinical<br>findings.<br>Same |
| Sample Type | Human serum and EDTA plasma | Same |
| Reagent<br>Packaging | 3 x 1 mL | Same |
| Reagent<br>Handling | Bottles placed directly on system | Reagents poured into reagent<br>containers |
| Units | mg/L | Same |
| Detection<br>Method | Nephelometry | Turbidimetry |
| Measurement | Quantitative | Same |
| Detection<br>Antibody | Monoclonal mouse anti-human FLC<br>kappa<br>Monoclonal mouse anti-antibody FLC<br>lambda | Same |
| Reagent<br>Composition | Polystyrene particles coated with<br>monoclonal antibodies | Same |
| Traceability | Internal Reference Plasma Pool | Same |
| | Predicate<br>Siemens Healthcare<br>BN Systems<br>N Latex FLC kappa<br>N Latex FLC lambda<br>(K171742, K182098) | Siemens Healthcare<br>Atellica® CH Analyzer<br>Modified Devices<br>N Latex FLC kappa<br>N Latex FLC lambda |
| Calibrators | One level | Same |
| Calibration<br>Interval | 42 days | Same |
| Analytical<br>Measuring<br>Range | Typical range:<br>kappa: 3.4 to 110 mg/L<br>lambda: 1.9 to 60 mg/L | kappa: 3.91 to 60 mg/L<br>lambda: 5.47 to 70 mg/L |
| Reference<br>Interval | kappa: 8.24 to 28.90 mg/L<br>lambda: 9.10 to 32.60 mg/L<br>Ratio: 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.