(16 days)
Immunological in vitro assay for quantitative determination of CA 15-3 in human serum, Li-heparin and EDTA plasma to aid in the management of breast cancer patients. In conjunction with other clinical and diagnostic procedures, serial testing with this assay is an aid
- · in the early detection of recurrence in previously treated stage II and III breast cancer patients
- · for monitoring response to therapy in metastatic breast cancer patients
The electrochemiluminescence immunoassay "ECLIA" is intended for use on cobas e immunoassay analyzers.
The Elecsys CA 15-3 II Test System is a two-step sandwich immunoassay with streptavidin microparticles and electrochemiluminescence detection for the quantitative determination of CA 15-3 in human serum, Li-heparin plasma and EDTA plasma. It is intended for use on the cobas e 801 immunoassay analyzer. The cobas e family of analyzers employs the electrochemiluminescence "ECLIA" technology. Results are determined using a calibration curve that is generated specifically on each instrument by a 2-point calibration and a master curve provided via the cobas link.
The provided text describes a 510(k) premarket notification for the Elecsys CA 15-3 II device, which is an immunological in vitro assay for the quantitative determination of CA 15-3. The primary purpose of this specific submission (K181492) is to extend the allowable sample type to include K2-EDTA plasma, in addition to serum and Li-heparin plasma already cleared under a previous submission (K171605).
Therefore, the acceptance criteria and study specifically relate to demonstrating the comparability of K2-EDTA plasma samples to serum samples for this assay. Most other performance characteristics (precision, analytical sensitivity, hook effect, linearity, endogenous interferences, method comparison to another analyzer, and stability) were demonstrated in the prior K171605 submission and are simply referenced, not re-evaluated in detail here, as the core assay technology remains the same.
Here's the breakdown of the information requested, focusing on the K2-EDTA plasma extension:
1. Table of Acceptance Criteria and Reported Device Performance
| Performance Characteristic | Acceptance Criteria (from context of K171605 and typical IVD validation) | Reported Device Performance (for K2-EDTA Plasma) |
|---|---|---|
| Comparability of K2-EDTA Plasma to Serum | Passing/Bablok regression analysis coefficients to represent comparable results (e.g., slope close to 1, intercept close to 0, high correlation coefficient). | Slope (95% CI): 0.985 (0.955–1.036) |
| Intercept (95% CI): -0.279 (-1.143–0.288) | ||
| Correlation Coefficient: 0.997 | ||
| Conclusion: The 44 serum/plasma pairs fulfilled the acceptance criteria for Passing Bablok Analysis. The data supports the addition of K2-EDTA plasma type. |
Note: The exact numerical acceptance criteria (e.g., specific ranges for slope and intercept) for Passing/Bablok regression are not explicitly stated in this document but are implied by the "fulfilled the acceptance criteria" statement. Typically, these would be pre-defined limits for non-inferiority or equivalence.
2. Sample Size Used for the Test Set and Data Provenance
- Sample Size: 44 serum/plasma paired samples.
- Data Provenance: The document does not explicitly state the country of origin for the samples. It is a retrospective study using existing samples, as they were "tested in singleton" for this specific comparison.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of those Experts
- This study does not involve expert human readers or ground truth established by subjective expert consensus (like in imaging studies). Instead, it's a quantitative immunoassay comparing instrument measurements from different sample types.
- The "ground truth" for this type of test is the measured value of the analyte (CA 15-3) in the serum sample, which is the established and currently accepted sample type. The study aims to show that the K2-EDTA plasma sample provides a comparable measurement.
4. Adjudication Method for the Test Set
- None. Adjudication methods (like 2+1, 3+1) are typically used in clinical or imaging studies where subjective interpretation is involved and consensus among multiple experts is needed to establish a definitive ground truth. This is a quantitative analytical performance study.
5. If a Multi Reader Multi Case (MRMC) Comparative Effectiveness Study was Done
- No. This is an analytical performance study of an in vitro diagnostic (IVD) device, not a multi-reader, multi-case clinical effectiveness study. It assesses the device's ability to measure an analyte accurately and comparably across different sample types, not how it impacts human reader performance or diagnostic accuracy in a clinical setting.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) was Done
- Yes, this is a standalone analytical performance study. The Elecsys CA 15-3 II assay itself provides a quantitative result. The study evaluated the direct output of the assay on the cobas e 801 analyzer for different sample types. There is no "human-in-the-loop" component in the direct measurement or comparison being assessed here.
7. The Type of Ground Truth Used
- The "ground truth" for comparison in this study is the measured CA 15-3 value in human serum, which is the currently accepted and validated sample matrix for this assay. The K2-EDTA plasma samples are being compared against these serum measurements to determine if they yield equivalent results. This implicitly relies on the established analytical accuracy of the device when using serum.
8. The Sample Size for the Training Set
- Not applicable / Not explicitly specified for this K2-EDTA plasma validation. This is an analytical validation study of a reagent/instrument system, not a machine learning model that requires a "training set" in the conventional sense. The "training" of the assay system itself comes from its development and standardization processes (e.g., against reference methods, master curves), which would have used numerous samples but are not detailed as a distinct "training set" in this context. The K171605 submission would have contained more foundational validation data.
9. How the Ground Truth for the Training Set Was Established
- Not applicable in the context of machine learning training data. For an IVD assay like this, the "ground truth" for its development and standardization (analogous to "training") is established through:
- Traceability to international standards or reference methods: The document states the method has been standardized against other established CA 15-3 methods (Enzymun-Test CA 15-3, CA 15-3 RIA from Fujirebio Diagnostics), indicating a chain of traceability to agreed-upon CA 15-3 values.
- Analytical precision and accuracy studies: Extensive studies are performed during development to ensure the assay consistently and accurately measures the target analyte over its dynamic range using known concentrations and reference materials.
- Clinical correlation: While not the focus of this specific K181492 submission, initial device development and validation (e.g., for K171605) would have involved clinical studies to correlate CA 15-3 levels with patient outcomes, disease status, and therapy response.
In summary, this 510(k) submission (K181492) is a targeted analytical validation to expand the Indications for Use for an existing immunoassay by demonstrating the analytical equivalence of an additional sample matrix (K2-EDTA plasma) to the previously cleared serum samples. The validation relies on quantitative comparisons rather than subjective human interpretation.
§ 866.6010 Tumor-associated antigen immunological test system.
(a)
Identification. A tumor-associated antigen immunological test system is a device that consists of reagents used to qualitatively or quantitatively measure, by immunochemical techniques, tumor-associated antigens in serum, plasma, urine, or other body fluids. This device is intended as an aid in monitoring patients for disease progress or response to therapy or for the detection of recurrent or residual disease.(b)
Classification. Class II (special controls). Tumor markers must comply with the following special controls: (1) A guidance document entitled “Guidance Document for the Submission of Tumor Associated Antigen Premarket Notifications (510(k)s) to FDA,” and (2) voluntary assay performance standards issued by the National Committee on Clinical Laboratory Standards.