(272 days)
The Kappa light chains assay is an in vitro diagnostic test used for the quantitative determination of immunoglobulin bound and free kappa light chains (KAPPA) in serum and in Li-heparin plasma by immunoturbidimetry on Synchron LX20 System. Measurement of type 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, in conjunction with other clinical and laboratory findings.
The Kappa light chains assay is an in vitro diagnostic test used for the quantitative determination of immunoglobulin bound and free kappa light chains (KAPPA) in serum and in Li-heparin plasma by immunoturbidimetry on Synchron LX20 System. The determination of Kappa light chains is based on the specific turbidimetric reaction, which occurs between a polyclonal antiserum against human Immunoglobulin Kappa light chains and its corresponding antigen under optimal pH conditions and in the presence of polyethylene glycol (PEG). The turbidity of the immune complex is proportional to the concentration of the analyte in the sample.
Here's an analysis of the provided text regarding the acceptance criteria and the study that proves the device meets those criteria:
Device: Kappa light chains assay (Sentinel)
Predicate Device: Beckman IMMAGE Immunochemistry System Kappa light chain (K964260)
1. Table of Acceptance Criteria and Reported Device Performance
The submission focuses on establishing substantial equivalence to a predicate device, primarily through performance similarities rather than explicit, pre-defined quantitative acceptance criteria with thresholds for accuracy, sensitivity, or specificity against a clinical ground truth. The acceptance is implied by acceptable correlation and precision compared to its own internal metrics and the overall 'similar performance characteristics' to the predicate.
| Performance Metric | Acceptance Criteria (Implied) | Reported Device Performance |
|---|---|---|
| Method Comparison (Correlation with Predicate) | "Acceptable correlation" with Beckman Kappa light chain (K964260) on IMMAGE nephelometer Analyzer. | Correlation coefficient (r): 0.985 |
| Slope (implied close to 1) | Slope: 0.900 | |
| Y-intercept (implied close to 0) | Y-intercept: 134 mg/dL | |
| Precision (Total Imprecision) | "Acceptable" %CV values. | Ranges from 2.4% to 6.8% CV across 6 levels. |
| Precision (Between Days) | "Acceptable" %CV values. | Ranges from 1.7% to 5.5% CV across 6 levels. |
| Precision (Repeatability) | "Acceptable" %CV values. | Ranges from 1.5% to 4.1% CV across 6 levels. |
| Analytical Measurement Range (AMR) - Lower Limit | Not explicitly stated but expected to be within a clinically relevant range. | Found lower limit: 31.2 mg/dL. Claimed: 35 mg/dL. |
| Analytical Measurement Range (AMR) - Upper Limit | Not explicitly stated but expected to be within a clinically relevant range. | Found upper limit: 750.13 mg/dL. Claimed: 750 mg/dL. |
2. Sample Size Used for the Test Set and Data Provenance
- Method Comparison: The document states "Comparative performance studies were conducted," but does not explicitly mention the sample size of patient samples used for the method comparison study. It does mention that the Kappa light chains assay on Synchron LX20 System was compared using "calibrator material with assigned Kappa Light chains concentration based on definition of Kappa Light chains as Whole IgG content (MW 150000)." This suggests that at least part of the comparison involved characterized calibrator samples rather than solely patient samples.
- Precision Studies: Two levels for 20x2x2 test (day x run x rep) on 6 levels implies:
- 20 days x 2 runs/day x 2 replicates/run = 80 measurements for each of the 6 levels.
- Total tests for precision: 6 levels * 80 tests/level = 480 tests.
- AMR Studies: Not explicitly stated.
- Data Provenance: The document does not specify the country of origin of the data or whether the studies were retrospective or prospective.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Their Qualifications
This type of in-vitro diagnostic (IVD) device (quantitative biochemical assay) does not typically rely on "experts" to establish ground truth in the same way an imaging or pathology device might. The "ground truth" for method comparison is the measurement obtained by the predicate device (Beckman IMMAGE Immunochemistry System Kappa light chain), which is itself a quantitative assay.
4. Adjudication Method for the Test Set
Not applicable. This is a comparison of quantitative measurements between two instruments/assays, not an interpretation that requires adjudication (like reading medical images).
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done, and Its Effect Size
No, a Multi-Reader Multi-Case (MRMC) comparative effectiveness study was not done. This type of study is relevant for devices where human readers interpret outputs (e.g., medical images), and the AI either assists or replaces human interpretation. This device is a quantitative diagnostic assay.
6. If a Standalone (Algorithm Only Without Human-in-the-Loop Performance) Was Done
Yes, the studies presented (method comparison, precision, AMR) are all standalone performance evaluations of the device (Kappa light chains assay on Synchron LX20 System). There is no "human-in-the-loop" component described for its operation or result generation; it's an automated in vitro diagnostic test system.
7. The Type of Ground Truth Used
The primary "ground truth" for the method comparison study was the measurements obtained from the predicate device (Beckman IMMAGE Immunochemistry System Kappa light chain, K964260). For precision and AMR, the ground truth refers to the intrinsic analytical performance characteristics of the new device itself, often evaluated against known concentrations or through repeated measurements, rather than an external clinical "ground truth" (e.g., pathology or outcomes data). The assays are also traceable to ERM-DA 470 (European Reference Material) from BCR (EG Community Bureau of Reference), corresponding to RPPHS (Reference Preparation for Protein in Human Serum), which serves as a metrological ground truth for standardization.
8. The Sample Size for the Training Set
The document does not specify a separate training set. For IVD submissions like this, the development process for an assay involves calibration and optimization, but typically, the pre-market submission focuses on the validation or test data for the final, locked-down assay. If there was an implicit "training" or development phase, the data used for that is not explicitly detailed as a distinct 'training set' in the context of machine learning.
9. How the Ground Truth for the Training Set Was Established
As no explicit "training set" is mentioned in the context of machine learning, this question isn't directly applicable. The assay's development (which could be considered analogous to training) would involve establishing appropriate calibration curves and reagent formulations based on known standards and reference materials (e.g., ERM-DA 470).
§ 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).