(90 days)
In-vitro diagnostic reagents for the quantitative determination of free light chains (FLC), type kappa or type lambda in human serum and EDTA-plasma by means of particle-enhanced immunonephelometry using the BN Systems. 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.
In-vitro diagnostic reagents for the quantitative determination of free light chains (FLC), type kappa or type lambda in human serum and EDTA-plasma by means of particle-enhanced immunonephelometry using the BN Systems. 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,
The 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 with samples containing FLC. 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. The devices in this submission have not materially changed since clearance under K171742. The purpose for this submission is to add monitoring of multiple myeloma (MM) to the intended use.
Here's a breakdown of the requested information based on the provided text, focusing on the expanded indication for monitoring Multiple Myeloma (MM) with the N Latex FLC kappa and N Latex FLC lambda assays:
1. Table of Acceptance Criteria and Reported Device Performance
The acceptance criteria are not explicitly stated as numerical targets in the document beyond the performance metrics themselves. However, the study aims to demonstrate substantial equivalence to the predicate device and satisfactory agreement with clinical status for MM monitoring. The reported performance is as follows:
| Performance Metric | Acceptance Criteria (Implied) | Reported Device Performance (N Latex FLC) |
|---|---|---|
| Clinical Status Comparison | Demonstrate adequate sensitivity and specificity for progression. | Sensitivity: 26% (12/47) (95% CI: 13.9% – 40.3%) for Progression |
| Specificity: 97% (335/344) (95% CI: 95.1%– 98.8%) for No Progression | ||
| Agreement with Clinical Assessment (Good Response) | High agreement with sCR/CR | 62% |
| Agreement with Clinical Assessment (Moderate Response) | High agreement with VGPR/PR | 79% |
| Agreement with Clinical Assessment (Stable Disease) | High agreement with SD | 70% |
| Agreement with Clinical Assessment (Progressive Disease) | High agreement with PD | 26% |
| Overall Agreement to Predicate (Response Category) | Demonstrate high agreement with the predicate device's classifications. | 89% agreement across all response categories. Higher for Good Response (100%) and Stable Disease (92%). |
Note: The document states "For the predicate device similar data were obtained when compared to clinical status," suggesting the 26% sensitivity for progression is considered acceptable in this context given the device's role as an "aid" in diagnosis and monitoring.
2. Sample Size Used for the Test Set and Data Provenance
- Sample Size for Test Set:
- Clinical Status Comparison: 391 patients (divided into 47 with Progression and 344 with No Progression).
- Agreement with Clinical Assessment: 391 patients.
- Comparison to Predicates (Response Category): 391 patients.
- Comparison to Predicates (Follow-up Graphs): 102 patients.
- Data Provenance: The study was a "multi-center study." The country of origin is not explicitly stated, but the submission is from Siemens Healthcare Diagnostics Products GmbH, based in Germany. The study appears to be retrospective as it compares results with existing clinical assessments and predicate device results.
3. Number of Experts Used to Establish Ground Truth for the Test Set and Qualifications
The document does not specify the number of experts or their qualifications for establishing the ground truth. It mentions "clinical assessment provided by the physician in charge within the Case Report Form (CRF)."
4. Adjudication Method for the Test Set
The document does not explicitly describe an adjudication method. "Clinical assessment provided by the physician in charge" suggests a singular clinical judgment rather than a consensus or adjudicated process among multiple experts for the ground truth.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
No, a Multi-Reader Multi-Case (MRMC) comparative effectiveness study was not performed. This device is an in-vitro diagnostic assay, not an imaging AI system that would typically involve human readers.
6. Standalone Performance
Yes, a standalone performance analysis was done. The N Latex FLC assays were evaluated independently in comparison to clinical status and then compared to the predicate devices. The sensitivity and specificity values are derived from the algorithm's performance in categorizing patient status.
7. Type of Ground Truth Used
The ground truth used was clinical assessment based on IMWG FLC criteria, taking into account IFE (immunofixation electrophoresis) and serum FLC measurements in conjunction with "other clinical findings" and "further information in addition to serum testing" as provided by the treating physician in the Case Report Form.
8. Sample Size for the Training Set
The document does not mention a training set. This is a diagnostic assay, and the study focuses on evaluating its performance (validation) rather than training an algorithm. The "training set" concept is more applicable to machine learning-based AI devices.
9. How the Ground Truth for the Training Set was Established
Not applicable, as no training set is described for this device.
§ 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).