(212 days)
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.
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 provided text describes the acceptance criteria and performance study for the Siemens Healthcare Diagnostics Products GmbH N Latex FLC kappa and N Latex FLC lambda assays when applied to the Atellica® CH Analyzer, specifically for the added indication as an aid in the evaluation of Monoclonal Gammopathy of Undetermined Significance (MGUS).
Here's a breakdown of the requested information:
1. Table of Acceptance Criteria and Reported Device Performance
The device performance is assessed through a method comparison study between the N Latex FLC kappa and N Latex FLC lambda assays on the Atellica® CH Analyzer (candidate device) and the N Latex FLC kappa and N Latex FLC lambda assays on the BN ProSpec System (predicate device).
| Acceptance Criteria | N Latex FLC Kappa Performance | N Latex FLC Lambda Performance | Acceptance Criteria Met? (Overall) |
|---|---|---|---|
| Pearson correlation coefficient: r ≥ 0.95 | 0.983 (Overall) 0.977 (MGUS samples only) | 0.970 (Overall) 0.970 (MGUS samples only) | Yes |
| Slope: 0.9 - 1.1 | 0.995 (Overall) 0.966 (MGUS samples only) | 0.914 (Overall) 0.841 (MGUS samples only) | Yes (Overall), No (Lambda MGUS) |
| Predicted bias: ≤ +/- 10% | |||
| Lower limit reference interval | 0.93% (Overall) 4.33% (MGUS samples only) | -7.60% (Overall) -15.7% (MGUS samples only) | Yes (Overall), No (Lambda MGUS) |
| Upper limit reference interval | -0.10% (Overall) -1.18% (MGUS samples only) | -8.56% (Overall) -16.9% (MGUS samples only) | Yes (Overall), No (Lambda MGUS) |
| Number of samples: n ≥ 160 | 212 (Overall) 38 (MGUS samples only) | 202 (Overall) 35 (MGUS samples only) | Yes (Overall), No (MGUS samples only meets criteria for specific MGUS analysis) |
Note on MGUS Specific Results: While the overall study meets the acceptance criteria for slope and predicted bias, the separate analysis for MGUS patients only for N Latex FLC lambda shows predicted biases of -15.7% and -16.9% at the lower and upper limit reference intervals respectively, and a slope of 0.841. These specific MGUS-only results for lambda do not meet the stated acceptance criteria of ≤ +/- 10% bias and a slope of 0.9-1.1. However, the document's general conclusion states "Acceptance criteria fulfilled" based on the overall results (Table 7.3.1-2 and 7.3.1-3). The separate MGUS-only table (7.3.1-4 and 7.3.1-5) is presented as a sub-analysis, and the acceptance criteria for this sub-analysis are not explicitly re-stated or modified from the general criteria. The FDA’s acceptance of this submission implies that the overall performance was considered sufficient.
2. Sample Size Used for the Test Set and Data Provenance
- Sample Size (Overall):
- N Latex FLC kappa: 212 samples
- N Latex FLC lambda: 202 samples
- Sample Size (MGUS-specific analysis):
- N Latex FLC kappa: 38 MGUS samples
- N Latex FLC lambda: 35 MGUS samples
- Data Provenance: The method comparison study was conducted internally at the Siemens Healthcare Diagnostics Products GmbH site in Marburg, Germany. It incorporated "samples derived from MGUS patients." The text for the clinical performance study for MGUS evaluation mentions "121 MGUS samples (89 Non-IgM, 21 IqM and 11 LC MGUS) and 102 polyclonal immunostimulation samples," but it's important to differentiate these from the test set numbers used in the method comparison study (212/202 and 38/35). The specific type (retrospective/prospective) is not explicitly stated for the source of these samples, but the mention of "derived from MGUS patients" suggests pre-existing samples, which would typically be retrospective.
3. Number of Experts Used to Establish Ground Truth for the Test Set and Qualifications of Experts
This information is not provided in the given text. The device is an in-vitro diagnostic reagent for quantitative determination of free light chains, and the "ground truth" for the method comparison study is established by comparison to a legally marketed predicate device (N Latex FLC assays on the BN ProSpec System).
4. Adjudication Method for the Test Set
This information is not applicable as the ground truth is established by a predicate diagnostic device, not by expert consensus or adjudication. The study is a method comparison, not a reader study.
5. If a Multi Reader Multi Case (MRMC) Comparative Effectiveness Study Was Done
No, an MRMC comparative effectiveness study was not done. This device is an in-vitro diagnostic assay, not an imaging AI device that relies on human reader interpretation. The study evaluates the analytical performance of the assay compared to a predicate, not how human readers improve with AI assistance.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done
Yes, in essence. This is a standalone performance study of the diagnostic assay on a new instrument platform (Atellica® CH Analyzer) compared to its performance on a predicate instrument (BN ProSpec System). The "algorithm" here refers to the analytical process of the in-vitro diagnostic test.
7. The Type of Ground Truth Used
The ground truth for the method comparison study is the performance of the predicate device (N Latex FLC kappa and N Latex FLC lambda assays on the BN ProSpec System). This is a comparative study aiming to show equivalence to an already legally marketed and accepted diagnostic method.
8. The Sample Size for the Training Set
This information is not provided in the text. The document describes a study to support a 510(k) submission for a diagnostic assay, which typically involves validation studies rather than "training sets" in the context of machine learning (unless the underlying technology uses machine learning, which is not indicated here). If there was any internal development or calibration process that could be considered "training," the sample size used for that is not disclosed.
9. How the Ground Truth for the Training Set Was Established
This information is not applicable/not provided as there is no mention of a "training set" in the context of machine learning. If the question refers to how the "predicate device" performance (which acts as the reference for this study) was originally established, that information is outside the scope of this particular 510(k) submission document. The predicate device itself has been cleared under previous 510(k)s (K171742, K182098, K193047, K201496).
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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
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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
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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 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 K201496 on October 29, 2021 as an aid in the monitoring of amyloidosis (AL) on the BN Systems.
| Trade Name | Common/UsualName | Classification | ProductCode | Panel | FDAclearance |
|---|---|---|---|---|---|
| N LatexFLC kappa | Immunoglobulin(light chain specific)immunological testsystem | Class II per21CFR866.5550 | DFH | Immunology(82) | K171742K182098K193047K201496 |
| N LatexFLC lambda | Immunoglobulin(light chain specific)immunological testsystem | Class II per21CFR866.5550 | DEH | Immunology(82) | K171742K182098K193047K201496 |
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.
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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)
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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): Table 8.-1: Similarities and Differences of Technologies between the BN Systems and the Atellica® CH Analyzer
| Predicate | Proposed | |
|---|---|---|
| Siemens HealthcareBN Systems | Siemens HealthcareAtellica® CH AnalyzerModified Devices | |
| N Latex FLC kappaN Latex FLC lambda(K171742, K182098, K193047,K201496) | N Latex FLC kappaN Latex FLC lambda | |
| Indicationsfor Use | N Latex FLC kappa and lambda are in-vitrodiagnostic reagents for the quantitativedetermination of free light chains (FLC),type kappa or type lambda in human serumand EDTA-plasma. N Latex FLC kappaandlambda assays are used:•as an aid in the diagnosis and monitoringof multiple myeloma (MM) on the BNSystems and Atellica® CH Analyzer. | N Latex FLC kappa and lambda are in-vitrodiagnostic reagents for the quantitativedetermination of free light chains (FLC), typekappa or type lambda in human serum andEDTA-plasma. N Latex FLC kappa andlambda assays are used:•as an aid in the diagnosis and monitoring ofmultiple myeloma (MM) on the BN Systemsand Atellica® CH Analyzer. |
| •as an aid in the diagnosis ofimmunoglobulin light-chain amyloidosis(AL) on the BN Systems and Atellica® CHAnalyzer. | •as an aid in the diagnosis ofimmunoglobulin light-chain amyloidosis (AL)on the BN Systems and Atellica® CHAnalyzer. | |
| •as an aid in the monitoring ofimmunoglobulin light-chain amyloidosis(AL) on the BN Systems. | •as an aid in the monitoring ofimmunoglobulin light-chain amyloidosis (AL)on the BN Systems. | |
| •as an aid in the evaluation of MonoclonalGammopathy of UndeterminedSignificance (MGUS) on the BN Systems. | •as an aid in the evaluation of MonoclonalGammopathy of Undetermined Significance(MGUS) on the BN Systems and Atellica®CH Analyzer. | |
| Results of FLC measurements shouldalways be interpreted in conjunction withother laboratory and clinical findings. | Results of FLC measurements shouldalways be interpreted in conjunction withother laboratory and clinical findings. | |
| SampleType | Human serum and EDTA plasma | Same |
| ReagentPackaging | 3 x 1 mL | Same |
| ReagentHandling | Bottles placed directly on system | Reagents poured into reagent containers |
| PredicateSiemens HealthcareBN SystemsN Latex FLC kappaN Latex FLC lambda(K171742, K182098, K193047,K201496) | ProposedSiemens HealthcareAtellica® CH AnalyzerModified DevicesN Latex FLC kappaN Latex FLC lambda | |
| 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 PlasmaPool | Same |
| Calibrators | One level | Same |
| CalibrationInterval | 42 days | Same |
| AnalyticalMeasuringRange | Typical range:kappa: 3.4 to 110 mg/Llambda: 1.9 to 60 mg/L (Calibrator lot valuedependent) | kappa: 3.91 to 60 mg/Llambda: 5.47 to 70 mg/L (Independent ofCalibrator lot value) |
| ReferenceInterval | kappa: 8.24 to 28.90 mg/Llambda: 9.10 to 32.60 mg/LRatio: 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.
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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.
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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 FLClambda on Atellica® CH Analyzer vsN Latex FLC kappa and N Latex FLClambda on BN ProSpec System | Pearson correlation coefficient:$r \ge 0.95$Slope : 0.9 - 1.1Predicted bias:• ≤ +/- 10% at lower limit reference interval• ≤ +/- 10% at upper limit reference intervalNumber of samples: $n \ge 160$ |
Table 7.3.1-2: Results Method comparison study
| Method | N | SamplerangeN LatexFLC mg/L | Slope(PassingBablok) | 95% CI(Slope) | YIntercept(PassingBablok) | 95% CI(Y-intercept) | Pearsoncorrelationcoefficient |
|---|---|---|---|---|---|---|---|
| Acceptancecriteria | ≥ 160 | N/A | 0.9 - 1.1 | N/A | N/A | N/A | $r \ge 0.95$ |
| N Latex FLCkappa | 212 * | 1.29- 550 | 0.995 | 0.982 – 1.02 | 0.119 | -0.223 - 0.346 | 0.983 |
| N Latex FLClambda | 202 ** | 1.85 – 710 | 0.914 | 0.887 - 0.939 | 0.112 | -0.252 - 0.525 | 0.970 |
| Acceptancecriteria 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 ofReference Interval[mg/L] | PredictedBias[%] | Upper Limit ofReference 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 | SamplerangeN LatexFLCmg/L | Slope(PassingBablok) | 95% Cl(Slope) | YIntercept(PassingBablok) | 95% Cl(Y-intercept) | Pearsoncorrelationcoefficient |
|---|---|---|---|---|---|---|---|
| N Latex FLCkappa | 38 | 6.61 - 345 | 0.966 | 0.930 - 1.00 | 0.645 | -0.207 - 1.19 | 0.977 |
| N Latex FLClambda | 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 ofReference Interval[mg/L] | Predicted Bias[%] | Upper Limit ofReferenceInterval [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.
END OF SUMMARY
§ 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).