(511 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.
Results of FLC measurements should always be interpreted in conjunction with other laboratory and clinical findings.
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 EDTAplasma. N Latex FLC kappa and lambda assays are used as an aid in the diagnosis and monitoring of multiple myeloma (MM) and immunoglobulin light-chain amyloidosis (AL) and as an aid in the evaluation of Monoclonal Gammopathy of Undetermined Significance (MGUS). Monitoring of immunoglobulin light-chain amyloidosis (AL) and evaluation of MGUS are cleared for use only on the BN Systems.
The N Latex FLC test systems are based upon the principles of particle-enhanced immunonephelometry. Polystyrene particles coated with monoclonal antibodies to human free light chains, type kappa or lambda, respectively, are agglutinated when mixed with samples containing free light chains. These aggregates scatter a beam of light passed through the sample. The intensity of the scattered light is proportional to the concentration of the respective protein in the sample. The result is evaluated by comparison with a standard of known concentration.
This document describes the N Latex FLC kappa and N Latex FLC lambda assays, in vitro diagnostic reagents used for the quantitative determination of free light chains (FLC), type kappa or type lambda, in human serum and EDTA plasma. This submission seeks to add "monitoring of immunoglobulin light-chain amyloidosis (AL) on the BN Systems" to the device's indications for use.
1. Acceptance Criteria and Reported Device Performance
The acceptance criteria are implicitly derived from the comparative studies presented, aiming to demonstrate substantial equivalence to the predicate device and acceptable concordance with clinical status. The reported performance is summarized in the tables below, using Evaluation Mode 2 as favored by Siemens.
Comparison of N Latex FLC versus Freelite (Predicate Device) - Evaluation Mode 2
| Response Criteria | Acceptance Criteria (Implicit) | Reported Performance (Agreement Rate) | 95% CI Bootstrap |
|---|---|---|---|
| Complete Response | High agreement | 68.1% | 53.6 – 86.3% |
| VGPR | High agreement | 81.8% | 67.4 – 91.1% |
| Partial Response | High agreement | 45.5% | 15.0 – 60.0% |
| Stable Disease | High agreement | 84.4% | 76.5 – 95.4% |
| Progressive Disease | High agreement | 88.2% | 70.0 – 100.0% |
| PPA (Progressive Disease) | High agreement | 88.2% (15/17) | 70.0 – 100.0% |
| NPA (Progressive Disease) | High agreement | 97.8% (219/224) | 95.9 - 99.6% |
Concordance of N Latex FLC versus Clinical Status - Evaluation Mode 2
| Response Criteria | Acceptance Criteria (Implicit) | Reported Performance (Concordance Rate) | 95% CI Bootstrap |
|---|---|---|---|
| Complete Response | High concordance | 52.9% | 25.0 – 74.3% |
| VGPR | High concordance | 71.4% | 56.6 – 88.9% |
| Partial Response | High concordance | 26.8% | 8.0 – 30.3% |
| Stable Disease | High concordance | 57.6% | 38.2 – 72.9% |
| Progressive Disease | High concordance | 70.6% | 47.1 – 88.2% |
| Sensitivity (Progressive Disease) | High sensitivity | 70.6% (12/17) | 47.1 – 88.2% |
| Specificity (Progressive Disease) | High specificity | 96.1% (197/205) | 94.8 - 99.0% |
2. Sample Size Used for the Test Set and Data Provenance
The test set for the comparative effectiveness study included data from a multi-center study on immunoglobulin light-chain amyloidosis (AL) patients.
- Sample Size: The N Latex FLC versus Freelite comparison involves a total of 241 observations based on initial and consecutive blood draws. The comparison to clinical status involves 222 observations.
- Data Provenance: The document does not explicitly state the country of origin. The study is retrospective, comparing changes between an initial sample draw and each consecutive blood draw, and then comparing these results to both a predicate device and clinical response.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
The "clinical response" used as ground truth was "provided by the physician taking into account all available clinical and laboratory information."
- Number of Experts: Not explicitly stated, but it implies individual physicians for each patient.
- Qualifications: "Physician" is the qualification mentioned. No specific experience levels (e.g., years of experience or specialization in oncology/hematology) are provided for these physicians.
4. Adjudication Method for the Test Set
The document mentions that clinical response was "provided by the physician taking into account all available clinical and laboratory information." There is no mention of a formal adjudication panel or process (e.g., 2+1, 3+1). The response evaluation criteria are derived from NCCN Response Criteria for serum M protein/IFE and FLC levels/ratios.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
No MRMC study was conducted. This device is an in-vitro diagnostic assay, not an imaging AI device that would typically involve human readers. The comparative effectiveness assessment focuses on the agreement between the new device and a predicate device, and the concordance of both devices with physician-determined clinical status.
6. Standalone (Algorithm Only Without Human-in-the-Loop Performance) Study
Yes, the studies presented are standalone performance assessments of the N Latex FLC kappa and lambda assays. The device itself is an automated assay, and its performance is evaluated directly (algorithm only). The comparison to clinical status is essentially an evaluation of the algorithm's output versus an established clinical truth.
7. Type of Ground Truth Used
The ground truth for the clinical comparison was based on clinical status/physician assessment, which encompasses "all available clinical and laboratory information" including NCCN Response Criteria. This is closer to an "outcomes data" or "expert consensus" type of ground truth in a clinical context.
8. Sample Size for the Training Set
The document does not provide information on the training set size. This submission focuses on performance data for an extended indication for monitoring AL. It refers to previous submissions (K171742, K182098, K193047) for established analytical and clinical studies, implying that the device was already developed and validated. The current submission's study used a distinct set of AL patients for evaluating the new monitoring claim.
9. How the Ground Truth for the Training Set Was Established
Not applicable/provided. As this submission is for an extended indication and refers to previous clearances for the device, details on the ground truth establishment for the initial training set (if any for algorithm development) are not included in this document. The focus of the provided text is on demonstrating performance for the new monitoring claim.
§ 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).