(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).
§ 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).