(212 days)
No
The device description details a particle-enhanced immunoassay using turbidimetry, which is a standard laboratory technique and does not mention any AI or ML components. The performance studies focus on method comparison and clinical performance using traditional statistical metrics.
No.
This device is an in-vitro diagnostic reagent used for quantitative determination of free light chains, which aids in the diagnosis and monitoring of multiple myeloma and amyloidosis. It does not provide therapy or treatment.
Yes
The "Intended Use / Indications for Use" section explicitly states that the device is "an aid in the diagnosis and monitoring of multiple myeloma (MM)," "an aid in the diagnosis of immunoglobulin light-chain amyloidosis (AL)," and "an aid in the evaluation of Monoclonal Gammopathy of Undetermined Significance (MGUS)." These are all diagnostic purposes.
No
The device description explicitly states it is an "in vitro diagnostic reagent" and describes a "particle-enhanced immunoassay determination" and "particle-enhanced turbidimetry," which are laboratory-based chemical and physical processes involving reagents and analyzers, not solely software.
Yes, this device is an IVD (In Vitro Diagnostic).
The "Intended Use / Indications for Use" section explicitly states: "N Latex FLC kappa and lambda are in-vitro diagnostic reagents for the quantitative determination of free light chains (FLC), type kappa or type lambda in human serum and EDTA-plasma."
The "Device Description" section also confirms this: "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..."
These statements clearly indicate that the device is intended for use in vitro (outside the body) to examine specimens (serum and EDTA plasma) for diagnostic purposes.
N/A
Intended Use / Indications for Use
N Latex FLC kappa and lambda are in-vitro diagnostic reagents for the quantitative determination of free light chains (FLC), type kappa or type lambda in human serum and EDTA-plasma. N Latex FLC kappa and lambda assays are used: • as an aid in the diagnosis and monitoring of multiple myeloma (MM) on the BN Systems and Atellica® CH Analyzer. • as an aid in the diagnosis of immunoglobulin light-chain amyloidosis (AL) on the BN Systems and Atellica® CH Analyzer. • as an aid in the monitoring of immunoglobulin light-chain amyloidosis (AL) on the BN Systems. · as an aid in the evaluation of Monoclonal Gammopathy of Undetermined Significance (MGUS) on the BN Systems and Atellica® CH Analyzer. Results of FLC measurements should always be interpreted in conjunction with other laboratory and clinical findings.
Product codes
DFH, DEH
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), as an aid in the diagnosis of amyloidosis (AL) on the BN Systems and Atellica® CH Analyzer; as an aid in the monitoring of amyloidosis (AL) on the BN Systems and as an aid in the evaluation of MGUS on the BN Systems.
The FLC test systems on the Atellica® CH Analyzer are based upon the principles of particle-enhanced turbidimetry. Polystyrene particles coated with antibodies to human free light chains, type kappa or lambda, respectively, are agglutinated with samples containing FLC. Monitoring the agglutination by measuring the increase in turbidity, a concentration curve is obtained. 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.
Mentions image processing
Not Found
Mentions AI, DNN, or ML
Not Found
Input Imaging Modality
Not Found
Anatomical Site
Not Found
Indicated Patient Age Range
Not Found
Intended User / Care Setting
Not Found
Description of the training set, sample size, data source, and annotation protocol
Not Found
Description of the test set, sample size, data source, and annotation protocol
For MGUS evaluation, the study was performed using 121 MGUS samples (89 Non-IgM, 21 IqM and 11 LC MGUS) and 102 polyclonal immunostimulation samples (confirmed with SPEP/ SIFE).
Summary of Performance Studies
Method comparison study: A Method comparison study designed according to CLSI EP09c: Measurement Procedure Comparison and Bias Estimation Using Patient Samples; Approved Guideline-Third Edition was conducted internally at the Siemens Healthcare Diagnostics Products GmbH site in Marburg, Germany. Method comparison data from K190879 was extended by inclusion of samples derived from MGUS patients in order to show equivalency for the new intended use population between the predicate the N Latex FLC kappa and N Latex FLC lambda assays on the BN ProSpec System and the candidate device the N Latex FLC kappa and N Latex FLC lambda assays on the Atellica® CH Analyzer. Clinical performance studies were performed for the predicate which has been recently cleared under K193047. The result showed positive rate of 50.4 % (61/121) for all MGUS samples tested and negative rate of 90.2 % (92/102) for non-MGUS samples.
Results for Method Comparison Study:
N Latex FLC kappa: N=212, Sample range: 1.29-550 mg/L, Slope: 0.995, 95% CI (Slope): 0.982-1.02, Y-Intercept: 0.119, 95% CI (Y-intercept): -0.223-0.346, Pearson correlation coefficient: 0.983.
N Latex FLC lambda: N=202, Sample range: 1.85-710 mg/L, Slope: 0.914, 95% CI (Slope): 0.887-0.939, Y-Intercept: 0.112, 95% CI (Y-intercept): -0.252-0.525, Pearson correlation coefficient: 0.970.
Results for Predicted Bias Analysis:
N Latex FLC kappa: Lower Limit of Reference Interval: 8.24 mg/L, Predicted Bias: 0.93%; Upper Limit of Reference Interval: 28.9 mg/L, Predicted Bias: -0.10%.
N Latex FLC lambda: Lower Limit of Reference Interval: 9.10 mg/L, Predicted Bias: -7.60%; Upper Limit of Reference Interval: 32.6 mg/L, Predicted Bias: -8.56%. All acceptance criteria were fulfilled.
Results for Method comparison study (MGUS patients only):
N Latex FLC kappa: N=38, Sample range: 6.61-345 mg/L, Slope: 0.966, 95% CI (Slope): 0.930-1.00, Y-Intercept: 0.645, 95% CI (Y-intercept): -0.207-1.19, Pearson correlation coefficient: 0.977.
N Latex FLC lambda: N=35, Sample range: 8.52-181 mg/L, Slope: 0.841, 95% CI (Slope): 0.750-0.934, Y-Intercept: 0.123, 95% CI (Y-intercept): -1.69-2.69, Pearson correlation coefficient: 0.970.
Predicted Bias Analysis (MGUS patients only):
N Latex FLC kappa: Lower Limit of Reference Interval: 8.24 mg/L, Predicted Bias: 4.33%; Upper Limit of Reference Interval: 28.9 mg/L, Predicted Bias: -1.18%.
N Latex FLC lambda: Lower Limit of Reference Interval: 9.10 mg/L, Predicted Bias: -15.7%; Upper Limit of Reference Interval: 32.6 mg/L, Predicted Bias: -16.9%.
Key Metrics
Positive rate of 50.4 % (61/121) for all MGUS samples tested and negative rate of 90.2 % (92/102) for non-MGUS samples.
Predicate Device(s)
Reference Device(s)
K171742, K182098, K193047, K190879
Predetermined Change Control Plan (PCCP) - All Relevant Information
Not Found
§ 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).
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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, which is a blue square with the letters "FDA" in white. To the right of the blue square is the text "U.S. FOOD & DRUG ADMINISTRATION" in blue.
March 2, 2022
Siemens Healthcare Diagnostics Products GmbH Martina Pfeiff Regulatory Affairs Manager Emil-von-Behring Str. 76 Marburg, 35041 Germany
Re: K212379
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: July 30, 2021 Received: August 2, 2021
Dear Martina Pfeiff:
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
1
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 803) for devices or postmarketing safety reporting (21 CFR 4, Subpart B) for combination products (see https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safety-reportingcombination-products); 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 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, Ph.D. Chief 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
2
Indications for Use
510(k) Number (if known) K212379
Device Name
N Latex FLC kappa and N Latex FLC lambda
Indications for Use (Describe)
N Latex FLC kappa and lambda are in-vitro diagnostic reagents for the quantitative determination of free light chains (FLC), type kappa or type lambda in human serum and EDTA-plasma. N Latex FLC kappa and lambda assays are used: • as an aid in the diagnosis and monitoring of multiple myeloma (MM) on the BN Systems and Atellica® CH Analyzer. • as an aid in the diagnosis of immunoglobulin light-chain amyloidosis (AL) on the BN Systems and Atellica® CH Analyzer.
• as an aid in the monitoring of immunoglobulin light-chain amyloidosis (AL) on the BN Systems.
· as an aid in the evaluation of Monoclonal Gammopathy of Undetermined Significance
(MGUS) on the BN Systems and Atellica® CH Analyzer.
Results of FLC measurements should always be interpreted in conjunction with other laboratory and clinical findings.
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)
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Image /page/3/Picture/1 description: The image shows the logo for Siemens Healthineers. The word "SIEMENS" is in teal, and the word "Healthineers" is in orange. To the right of the word "Healthineers" is a series of orange dots arranged in a circular pattern.
510(k) Summary per 21 CFR 807.92 Type of 510(k): Traditional 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: K212379
1. Submitter
Siemens Healthcare Diagnostics Products GmbH Emil-von-Behring-Str. 76 35041 Marburg, Germany
| Contact Person: | Martina Pfeiff |
|---|---|
| Email : | martina.pfeiff@siemens-healthineers.com |
| Phone: | +49 (174) 3319336 |
| Date of Preparation: | July 30, 2021 |
2. Device Information
| Proprietary Name: | N Latex FLC kappa assay
N 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 21CFR
866.5550 |
| Regulatory Class: | II |
| 510(k) Review Panel: | Clinical Immunology (82) |
4
3. Legally Marketed Unmodified / Predicate Devices
Cleared for use on Siemens' BN Systems under K201496 on October 29, 2021 as an aid in the monitoring of amyloidosis (AL) on the BN Systems.
| Trade Name | Common/Usual
Name | Classification | Product
Code | Panel | FDA
clearance |
|-----------------------|--------------------------------------------------------------------------|-----------------------------------|-----------------|--------------------|------------------------------------------|
| N Latex
FLC kappa | Immunoglobulin
(light chain specific)
immunological test
system | Class II per
21CFR
866.5550 | DFH | Immunology
(82) | K171742
K182098
K193047
K201496 |
| N Latex
FLC lambda | Immunoglobulin
(light chain specific)
immunological test
system | Class II per
21CFR
866.5550 | DEH | Immunology
(82) | K171742
K182098
K193047
K201496 |
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), as an aid in the diagnosis of amyloidosis (AL) on the BN Systems and Atellica® CH Analyzer; as an aid in the monitoring of amyloidosis (AL) on the BN Systems and as an aid in the evaluation of MGUS on the BN Systems.
The FLC test systems on the Atellica® CH Analyzer are based upon the principles of particle-enhanced turbidimetry. Polystyrene particles coated with antibodies to human free light chains, type kappa or lambda, respectively, are agglutinated with samples containing FLC. Monitoring the agglutination by measuring the increase in turbidity, a concentration curve is obtained. 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.
The devices in this submission are not materially changed from those since clearance under K171742. Later clearances dealt with the intended use claims. The purpose for this submission is to add an aid in the evaluation of Monoclonal Gammopathy of Undetermined Significance (MGUS) claim, on the Atellica® CH Analyzer to the intended use.
5
5. Intended Use / Indications for Use
N Latex FLC kappa and N Latex FLC lambda assays
N Latex FLC kappa and lambda are in-vitro diagnostic reagents for the quantitative determination of free light chains (FLC), type kappa or type lambda in human serum and EDTA-plasma. N Latex FLC kappa and lambda assays are used:
. as an aid in the diagnosis and monitoring of multiple myeloma (MM) on the BN Systems and Atellica® CH Analyzer.
as an aid in the diagnosis of immunoglobulin light-chain amyloidosis (AL) on the BN . Systems and Atellica® CH Analyzer.
as an aid in the monitoring of immunoglobulin light-chain amyloidosis (AL) on the BN . Systems.
as an aid in the evaluation of Monoclonal Gammopathy of Undetermined Significance . (MGUS) on the BN Systems and Atellica® CH Analyzer.
Results of FLC measurements should always be interpreted in conjunction with other laboratory and clinical findings.
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. The values of FLC kappa or FLC lambda on BN systems and on Atellica® CH Analyzer should not be used interchangeably.
If, in the course of monitoring a patient, the assay method used for determining serial levels of the FLC kappa and FLC lambda is changed, the laboratory MUST perform additional testing to confirm baseline values prior to changing assays.
Precaution:
. The performance of N Latex FLC kappa and lambda has not been thoroughly studied in IgM and Light Chain MGUS patients due to the low prevalence of these subtypes.
. Patients with decreased renal function (e.g. chronic kidney disease) may have elevated FLC kappa and FLC lambda.
Sample populations excluded MGUS populations that were further diagnosed with a . disease/disorder in subsequent testing with another medical device such as human immunodeficiency virus, hepatitis, and chronic lymphocytic leukemia. Thus, because the samples were enriched the specificity of the test may be inflated.
7. Special instrument requirements:
Atellica® CH Analyzer (K151767) BN II System (K943997) BN ProSpec® (K001647)
6
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): Table 8.-1: Similarities and Differences of Technologies between the BN Systems and the Atellica® CH Analyzer
| Predicate | Proposed | |
|---|---|---|
| Siemens Healthcare | ||
| BN Systems | Siemens Healthcare | |
| Atellica® CH Analyzer | ||
| Modified Devices | ||
| N Latex FLC kappa | ||
| N Latex FLC lambda | ||
| (K171742, K182098, K193047, | ||
| K201496) | N Latex FLC kappa | |
| N Latex FLC lambda | ||
| Indications | ||
| for Use | N Latex FLC kappa and lambda are in-vitro | |
| diagnostic reagents for the quantitative | ||
| determination of free light chains (FLC), | ||
| type kappa or type lambda in human serum | ||
| and EDTA-plasma. N Latex FLC kappaand | ||
| lambda assays are used: | ||
| •as an aid in the diagnosis and monitoring | ||
| of multiple myeloma (MM) on the BN | ||
| Systems and Atellica® CH Analyzer. | N Latex FLC kappa and lambda are in-vitro | |
| diagnostic reagents for the quantitative | ||
| determination of free light chains (FLC), type | ||
| kappa or type lambda in human serum and | ||
| EDTA-plasma. N Latex FLC kappa and | ||
| lambda assays are used: | ||
| •as an aid in the diagnosis and monitoring of | ||
| multiple myeloma (MM) on the BN Systems | ||
| and Atellica® CH Analyzer. | ||
| •as an aid in the diagnosis of | ||
| immunoglobulin light-chain amyloidosis | ||
| (AL) on the BN Systems and Atellica® CH | ||
| Analyzer. | •as an aid in the diagnosis of | |
| immunoglobulin light-chain amyloidosis (AL) | ||
| on the BN Systems and Atellica® CH | ||
| Analyzer. | ||
| •as an aid in the monitoring of | ||
| immunoglobulin light-chain amyloidosis | ||
| (AL) on the BN Systems. | •as an aid in the monitoring of | |
| immunoglobulin light-chain amyloidosis (AL) | ||
| on the BN Systems. | ||
| •as an aid in the evaluation of Monoclonal | ||
| Gammopathy of Undetermined | ||
| Significance (MGUS) on the BN Systems. | •as an aid in the evaluation of Monoclonal | |
| Gammopathy of Undetermined Significance | ||
| (MGUS) on the BN Systems and Atellica® | ||
| CH Analyzer. | ||
| Results of FLC measurements should | ||
| always be interpreted in conjunction with | ||
| other laboratory and clinical findings. | Results of FLC measurements should | |
| always be interpreted in conjunction with | ||
| other laboratory and clinical findings. | ||
| SampleType | Human serum and EDTA plasma | Same |
| Reagent | ||
| Packaging | 3 x 1 mL | Same |
| Reagent | ||
| Handling | Bottles placed directly on system | Reagents poured into reagent containers |
| Predicate | ||
| Siemens Healthcare | ||
| BN Systems | ||
| N Latex FLC kappa | ||
| N Latex FLC lambda | ||
| (K171742, K182098, K193047, | ||
| K201496) | Proposed | |
| Siemens Healthcare | ||
| Atellica® CH Analyzer | ||
| Modified Devices | ||
| N Latex FLC kappa | ||
| N Latex FLC lambda | ||
| Detection | ||
| Method | Nephelometry | Turbidimetry |
| Measurement | Quantitative | Same |
| Detection | ||
| Antibody | Monoclonal mouse anti-human FLC | |
| kappa | ||
| Monoclonal mouse anti-antibody FLC | ||
| lambda | Same | |
| Reagent | ||
| Composition | Polystyrene particles coated with | |
| monoclonal antibodies | Same | |
| Traceability | Internal Reference Plasma | |
| Pool | Same | |
| Calibrators | One level | Same |
| Calibration | ||
| Interval | 42 days | Same |
| Analytical | ||
| Measuring | ||
| Range | Typical range: | |
| kappa: 3.4 to 110 mg/L | ||
| lambda: 1.9 to 60 mg/L (Calibrator lot value | ||
| dependent) | kappa: 3.91 to 60 mg/L | |
| lambda: 5.47 to 70 mg/L (Independent of | ||
| Calibrator lot value) | ||
| Reference | ||
| Interval | kappa: 8.24 to 28.90 mg/L | |
| lambda: 9.10 to 32.60 mg/L | ||
| Ratio: 0.53 to 1.51 | Same |
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Results of FLC measurements should always be interpreted in conjunction with other laboratory and clinical findings.
The purpose of the modification to the proposed device is to add the aid in evaluation of Monoclonal Gammopathy of Undetermined Significance (MGUS) to the intended use for the reagent application on the Atellica® CH Analyzer.
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.
8
7.1 Risk Analysis
Risk analysis was performed according to the ISO14971:2019 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 add the aid in evaluation of MGUS to the intended use. 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 acceptable degree.
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 to demonstrate comparability between N Latex FLC kappa and lambda on the Atellica® CH Analyzer and N Latex FLC kappa and lambda on the BN ProSpec System are presented in section 7.3.
Reagent and application specific performance claims established in K171742 and K182098 for the reagent application on the BN systems and K190879 for the reagent application on the Atellica® CH Analyzer are not affected by the change to the intended use of the reagent and remain unchanged for K193047 and for this submission.
7.3. Performance Studies
7.3.1 Method comparison study
Summary of the protocol:
A Method comparison study designed according to CLSI EP09c: Measurement Procedure Comparison and Bias Estimation Using Patient Samples; Approved Guideline-Third Edition was conducted internally at the Siemens Healthcare Diagnostics Products GmbH site in Marburg, Germany.
Method comparison data from K190879 was extended by inclusion of samples derived from MGUS patients in order to show equivalency for the new intended use population between the predicate the N Latex FLC kappa and N Latex FLC lambda assays on the BN ProSpec System and the candidate device the N Latex FLC kappa and N Latex FLC lambda assays on the Atellica® CH Analyzer.
Clinical performance studies were performed for the predicate which has been recently cleared under K193047.
For MGUS evaluation, the study was performed using 121 MGUS samples (89 Non-IgM, 21 IqM and 11 LC MGUS) and 102 polyclonal immunostimulation samples (confirmed with SPEP/ SIFE). The result showed positive rate of 50.4 % (61/121) for all MGUS samples tested and negative rate of 90.2 % (92/102) for non-MGUS samples.
9
Summary of the Results:
The correlation between the assays is summarized below.
Table 7.3.1-1: Acceptance criteria Method comparison study
| Method | Acceptance Criteria |
|---|---|
| N Latex FLC kappa and N Latex FLC | |
| lambda on Atellica® CH Analyzer vs | |
| N Latex FLC kappa and N Latex FLC | |
| lambda on BN ProSpec System | Pearson correlation coefficient: |
| $r \ge 0.95$ | |
| Slope : 0.9 - 1.1 |
Predicted bias:
• ≤ +/- 10% at lower limit reference interval
• ≤ +/- 10% at upper limit reference interval
Number of samples: $n \ge 160$ |
Table 7.3.1-2: Results Method comparison study
| Method | N | Sample
range
N Latex
FLC mg/L | Slope
(Passing
Bablok) | 95% CI
(Slope) | Y
Intercept
(Passing
Bablok) | 95% CI
(Y-intercept) | Pearson
correlation
coefficient |
|----------------------------------|--------|----------------------------------------|------------------------------|-------------------|---------------------------------------|-------------------------|---------------------------------------|
| Acceptance
criteria | ≥ 160 | N/A | 0.9 - 1.1 | N/A | N/A | N/A | $r \ge 0.95$ |
| N Latex FLC
kappa | 212 * | 1.29- 550 | 0.995 | 0.982 – 1.02 | 0.119 | -0.223 - 0.346 | 0.983 |
| N Latex FLC
lambda | 202 ** | 1.85 – 710 | 0.914 | 0.887 - 0.939 | 0.112 | -0.252 - 0.525 | 0.970 |
| Acceptance
criteria fulfilled | yes | N/A | yes | N/A | N/A | N/A | yes |
*including 38 MGUS samples
**including 35 MGUS samples
Table 7.3.1-3: Predicted Bias Analysis- Method comparison study
| Method | Lower Limit of
Reference Interval
[mg/L] | PredictedBias
[%] | Upper Limit of
Reference Interval
[mg/L] | PredictedBias
[%] |
|-------------------------------|------------------------------------------------|----------------------|------------------------------------------------|----------------------|
| Acceptance criteria | -- | $\leq$ +/- 10 | -- | $\leq$ +/- 10 |
| N Latex FLC kappa | 8.24 | 0.93 | 28.9 | -0.10 |
| N Latex FLC lambda | 9.10 | -7.60 | 32.6 | -8.56 |
| Acceptance criteria fulfilled | -- | yes | -- | yes |
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| Method | N | Sample
range
N Latex
FLCmg/L | Slope
(Passing
Bablok) | 95% Cl
(Slope) | Y
Intercept
(Passing
Bablok) | 95% Cl
(Y-intercept) | Pearson
correlation
coefficient |
|-----------------------|----|---------------------------------------|------------------------------|-------------------|---------------------------------------|-------------------------|---------------------------------------|
| N Latex FLC
kappa | 38 | 6.61 - 345 | 0.966 | 0.930 - 1.00 | 0.645 | -0.207 - 1.19 | 0.977 |
| N Latex FLC
lambda | 35 | 8.52 - 181 | 0.841 | 0.750 - 0.934 | 0.123 | -1.69 - 2.69 | 0.970 |
Table 7.3.1-4: Results Method comparison study (MGUS patients only)
Table 7.3.1-5: Predicted Bias Analysis- Method comparison study (MGUS patients only)
| Method | Lower Limit of
Reference Interval
[mg/L] | Predicted Bias
[%] | Upper Limit of
Reference
Interval [mg/L] | Predicted Bias
[%] |
|--------------------|------------------------------------------------|-----------------------|------------------------------------------------|-----------------------|
| N Latex FLC kappa | 8.24 | 4.33 | 28.9 | -1.18 |
| N Latex FLC lambda | 9.10 | -15.7 | 32.6 | -16.9 |
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.