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510(k) Data Aggregation
(626 days)
The FLC Kappa kit is intended for the quantification of Kappa free light chains in human serum from adults with an Enzyme-Linked Immunosorbent Assay (ELISA) procedure. Measurement of free light chains aids in the diagnosis of multiple myeloma and AL amyloidosis. It must be used in conjunction with other laboratory and clinical findings. For In Vitro Diagnostic Use.
The FLC Lambda kit is intended for the quantification of Lambda free light chains in human serum from adults with an Enzyme-Linked Immunosorbent Assay (ELISA) procedure. Measurement of free light chains aids in the diagnosis of multiple myeloma and AL amyloidosis. It must be used in conjunction with other laboratory and clinical findings. For In Vitro Diagnostic Use.
The FLC Kappa and FLC Lambda test kits are intended for the quantification of free light chains in human serum from adults with an Enzyme-Linked Immunosorbent Assay (ELISA) procedure utilizing specific antibodies targeting anti-Lambda free light chains. It is carried out in 8 successive steps: Incubation of the previously diluted samples and calibrators, in the wells of the microplate, where specific free light chain antibodies are fixed. Washing of the wells to remove elements that have not been fixed by the anti-free light chain antiserum. Incubation with an anti- light chain antiserum (Kit specific) conjugated to peroxidase. Washing of the wells to remove the excess of antiserum conjugated to peroxidase. Incubation with peroxidase substrate. Stopping of the enzymatic reaction with an acidic solution. Reading of the optical density by absorbance spectrophotometry at 450 nm of the colored product. Calculation of the free light chain concentration of the sample using a calibration curve obtained with calibrators that have been analyzed on the same microplate.
Here's a breakdown of the acceptance criteria and study details for the Sebia FLC Kappa and FLC Lambda kits, based on the provided FDA 510(k) summary.
Note: This document describes an in vitro diagnostic (IVD) device, which measures specific analytes (free light chains) in human serum using a laboratory assay (ELISA). The concepts of "AI assistance," "human readers," "radiologist," and "image" are not relevant to this type of device. Therefore, sections pertaining to these concepts (like MRMC studies) are not applicable and will be marked as such. The "ground truth" for an IVD kit is established through various analytical performance studies demonstrating its accuracy and reliability compared to established methods, and clinical studies correlating its results with disease states.
Acceptance Criteria and Device Performance for Sebia FLC Kappa and FLC Lambda Kits
1. Table of Acceptance Criteria & Reported Device Performance
The FDA 510(k) summary does not explicitly present a "table of acceptance criteria" in the format of pass/fail thresholds. Instead, it details various performance studies and their results, which implicitly form the basis for acceptance. The reported device performance is indicated by the successful execution of these studies and the obtained values meeting recognized clinical laboratory standards (e.g., CLSI guidelines).
General Performance Categories and Key Findings:
| Performance Category | Acceptance Criteria (Implicit from CLSI Guidelines/Industry Norms) | Reported Device Performance (Key Findings) |
|---|---|---|
| Precision (Reproducibility) | Low Coefficient of Variation (CV%) across various conditions (within-run, between-runs, within-day, between-days, operators, lots, sites). Generally, CV% should be within acceptable limits for diagnostic assays. | FLC Kappa: Total %CVs for single-site, multi-operator, multi-lot, and multi-site reproducibility studies were generally below 15% across various sample concentrations, which is typical for acceptable immunoassay precision. FLC Lambda: Similar to Kappa, total %CVs across various reproducibility studies were generally below 15%, demonstrating acceptable precision. (e.g., Multi-site total reproducibility: 11.4% to 15.2%) |
| Linearity/Assay Range | Demonstrated linearity across the claimed analytical measuring range, with slopes near 1 and intercepts near 0 for linear regression. | FLC Kappa: Linear between 4.5 mg/L and 76.2 mg/L. Three panels showed linear regressions with slopes close to 1 (e.g., Y=1.009x -0.2967, Y=1.016x -0.2014, Y=0.9332x + 0.4952) and small Y-intercepts. FLC Lambda: Linear between 3.8 mg/L and 66.8 mg/L. Three panels showed linear regressions with slopes close to 1 (e.g., Y=1.046x -1.537, Y=0.9561x -0.62, Y=0.9611x -0.31) and small Y-intercepts. |
| Limits (LOB, LOD, LOQ) | Limits of Blank (LOB), Detection (LOD), and Quantitation (LOQ) must be established and clinically relevant. LOQ typically related to imprecision (e.g., <20% CV). | FLC Kappa: LOB = 0 mg/L, LOD = 0.8 mg/L, LOQ = 4.5 mg/L. FLC Lambda: LOB = 0 mg/L, LOD = 1.1 mg/L, LOQ = 3.8 mg/L. LOQ defined as lowest concentration with <20% within-laboratory imprecision. |
| Hook Effect | No significant Hook effect (antigen excess) within the expected clinical range. | No interference driven by the Hook effect was observed. |
| Analytical Specificity (Interferences) | No significant interference from common biological substances or drugs at clinically relevant concentrations. | No interference detected from conjugated/unconjugated bilirubin, total protein, hemoglobin, triglycerides, rheumatoid factor, or specified drugs (melphalan, dexamethasone, daratumumab, bortezomib, lenalidomide, pomalidomide, carfilzomib, isatuximab) at tested levels. |
| Stability | Kits and controls must maintain stated performance over their claimed shelf-life and in-use periods. | FLC Kappa & Lambda Kits: Shelf life: 9 months at 2-8°C. In-use: 5 uses within 1 month and 15 cumulative hours maximum at room temperature (19-25°C). All results met stability acceptance criteria. |
| Method Comparison (Quantitative) | Demonstrated agreement with a legally marketed predicate device (Siemens BN™ II Freelite® assays), often assessed by regression analysis (slope, intercept, R2). | FLC Kappa (vs. predicate): N=216, Sample Range 1.0-1947.0 mg/L. Slope: 0.557 (95% CI: 0.5125-0.6021), Y-Intercept: 0.912 (95% CI: 0.752-1.072), R2: 0.917. FLC Lambda (vs. predicate): N=221, Sample Range 1.6-860.4 mg/L. Slope: 0.608 (95% CI: 0.5224-0.6937), Y-Intercept: 2.243 (95% CI: 1.149-3.337), R2: 0.749. Note: Slopes deviate significantly from 1, indicating a proportional bias. This is common when comparing different assay methods and platforms, and is acceptable as long as the correlation is strong and clinical utility is demonstrated. |
| Method Comparison (Qualitative - Ratio) | Acceptable Positive Percent Agreement (PPA) and Negative Percent Agreement (NPA) with the predicate for the KFLC/LFLC ratio. | Kappa FLC / Lambda FLC Ratio (vs. predicate): PPA = 82.3%, NPA = 89.3%. (N=216 serum samples). |
| Clinical Performance (Sensitivity/Specificity) | Acceptable clinical sensitivity and specificity for indicated conditions (multiple myeloma, AL amyloidosis), demonstrated by correlation with clinical diagnosis. | Multiple Myeloma (N=366): Clinical sensitivity: 96.6% (95% CI: 94.0%-99.3%), Clinical specificity: 85.1% (95% CI: 79.4%-89.5%).AL Amyloidosis (N=333): Clinical sensitivity: 91.0% (95% CI: 86.3%-95.7%), Clinical specificity: 85.1% (95% CI: 79.4%-89.5%). |
| Reference Range | Established reference intervals for healthy populations. | US-population (N=238 healthy adults): Kappa FLC: 6.4 - 17.4 mg/L. Lambda FLC: 8.4 - 21.8 mg/L. Kappa FLC / Lambda FLC ratio: 0.46 - 1.51. |
2. Sample Sizes and Data Provenance
- Precision (Reproducibility):
- Single-site: 6 samples per kit (4 serum, 2 controls), 3 replicates/sample, 20 days, 2 runs/day = 120 results per sample.
- Multi-operator: 6 samples per kit (4 serum, 2 controls), 5 replicates/sample, 5 days, 3 operators = 75 results per sample.
- Multi-lot: 6 samples per kit (4 serum, 2 controls), 5 replicates/sample, 5 days, 3 lots = 75 results per sample.
- Multi-site: 6 samples per kit (4 serum, 2 controls), 5 replicates/sample, 5 days, 3 sites (3 operators).
- Linearity: 3 patient sample pools for each FLC assay (Kappa, Lambda). Number of individual samples/aliquots per pool not specified, but typically involves serial dilutions.
- LOD/LOQ: 5 low-concentration samples, tested in 2 runs of 4 replicates over 7 days using 2 reagent lots (56 replicates/sample/lot).
- Method Comparison (Quantitative): 216 serum samples (Kappa), 221 serum samples (Lambda).
- Method Comparison (Qualitative - Ratio): 216 serum samples.
- Reference Range: 238 apparently healthy adults (US-population).
- Clinical Study: 510 samples total (177 Multiple Myeloma, 144 AL Amyloidosis, 189 non-myeloma/non-amyloidosis subjects with various clinical conditions).
- Data Provenance: The document explicitly states the reference range study was conducted on a "US-population." The clinical study involved samples from various clinical conditions, implying real-world patient data, likely retrospective given the disease categories. The other analytical studies were performed in a controlled laboratory setting. The exact countries of origin for all samples beyond the US reference range study are not specified, but the manufacturing site is in France, suggesting international collaboration or testing. All studies appear to be prospective in their design for generating the performance data for the submission.
3. Number of Experts & Qualifications for Ground Truth
This is an IVD device, not an AI image analysis device. As such, there are no "experts" in the sense of radiologists providing interpretations for AI model ground truth. The "ground truth" for the performance studies is established by:
- Reference Methods: Comparison studies use a predicate device (The Binding Site Freelite® Human Kappa/Lambda Free kits on Siemens BN™ II) as a reference.
- Established CLSI Guidelines: All analytical studies (precision, linearity, limits, interference) follow rigorous Clinical and Laboratory Standards Institute (CLSI) guidelines (e.g., EP05-A3, EP06-ed2, EP17-A2, EP7-A2, EP09-A3, EP28-A3c). Compliance with these guidelines, developed by consensus among clinical laboratory experts, forms the basis for acceptable performance.
- Clinical Diagnosis: For the clinical study, the "ground truth" for multiple myeloma and AL amyloidosis was the clinical diagnosis of the patients. This diagnosis would be established by medical specialists (e.g., hematologists, oncologists) based on a comprehensive evaluation of laboratory findings, biopsy results, imaging, and clinical presentation. No specific number of such adjudicating clinicians is provided.
4. Adjudication Method for the Test Set
Not applicable in the context of an IVD device measuring analytes. The ground truth for analytical performance is adherence to validated laboratory procedures and statistical analysis per CLSI guidelines, and for clinical performance, it's the established clinical diagnosis for the patient samples.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
Not applicable. This is an in vitro diagnostic assay, not an AI-assisted diagnostic imaging device that involves human readers interpreting images with or without AI.
6. Standalone Performance
Yes, the entire performance data provided (precision, linearity, limits, interference, stability, quantitative and qualitative comparisons) represents the standalone performance of the Sebia FLC Kappa and FLC Lambda ELISA kits. The results are generated directly by the assay without human interpretation of complex outputs like images. The only "human-in-the-loop" aspect is the performance of the laboratory testing, which is standardized by the kit's instructions for use and quality control.
7. Type of Ground Truth Used
- Analytical Performance: Ground truth derived from established laboratory reference methods (e.g., predicate device for comparison), consensus guidelines (CLSI), and defined metrological properties (e.g., purified standards for linearity, known low-concentration samples for LOD/LOQ).
- Clinical Performance: "Ground truth" for the clinical study was the clinical diagnosis (Multiple Myeloma and AL Amyloidosis) of the patients from whom the serum samples were collected. This is based on comprehensive clinical and laboratory findings, not a single test.
8. Sample Size for the Training Set
Not applicable. This is not an AI/machine learning device that requires a training set. This is a traditional IVD ELISA assay.
9. How the Ground Truth for the Training Set Was Established
Not applicable, as there is no "training set" for this type of IVD device.
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