(39 days)
The Access BR Monitor assay is a paramagnetic particle, chemiluminescent immunoassay for the quantitative determination of CA 15-3 antigen levels in human serum and plasma using the Access Immunoassay Systems. This device is indicated for use in the measurement of CA 15-3 antigen to aid in the management of breast cancer patients. Serial testing for patient CA 15-3 antigen concentrations should be used in conjunction with other clinical methods for monitoring breast cancer.
The Access BR Monitor Calibrators are intended to calibrate the Access BR Monitor assay for the quantitative determination of CA 15-3 antigen levels in human serum and plasma using the Access Immunoassay Systems.
The Access BR Monitor assay and the Access Immunoassay Analyzers comprise the Access Immunoassay Systems for the quantitative determination of CA 15-3 antigen levels in human serum and plasma.
Acceptance Criteria and Device Performance Study for Access® BR Monitor Assay (K072612)
This submission describes the modified Access® BR Monitor assay, an immunoassay for the quantitative determination of CA 15-3 antigen levels in human serum and plasma. The study focuses on demonstrating substantial equivalence to the previously cleared Access® BR Monitor assay (K033036) by verifying that the modified device meets specified acceptance criteria, particularly concerning imprecision.
1. Table of Acceptance Criteria and Reported Device Performance
| Attribute | Acceptance Criteria (Modified Device) | Reported Device Performance (Modified Device) |
|---|---|---|
| Intended Use | For the quantitative determination of CA 15-3 antigen levels in human serum and plasma. | For the quantitative determination of CA 15-3 antigen levels in human serum and plasma. (Meets Acceptance Criteria) |
| Assay principles | Is a two-site immunoenzymatic ("sandwich") assay. | Is a two-site immunoenzymatic ("sandwich") assay. (Meets Acceptance Criteria) |
| Solid Support | Paramagnetic particles. | Paramagnetic particles. (Meets Acceptance Criteria) |
| Detection System | Chemiluminescent substrate. | Chemiluminescent substrate. (Meets Acceptance Criteria) |
| Calibrator | Six levels of CA 15-3 antigen at levels of zero and approximately 10, 50, 100, 500, and 1000 U/mL in a buffered BSA matrix. | Six levels of CA 15-3 antigen at levels of zero and approximately 10, 50, 100, 500, and 1000 U/mL in a buffered BSA matrix. (Meets Acceptance Criteria) |
| Analytical Range | 0.5 - 1000 U/mL | 0.5 - 1000 U/mL (Meets Acceptance Criteria) |
| Imprecision | ≤ 10% for concentrations between 15 and 500 U/mL, and ≤ 12% for concentrations greater than 500 U/mL. | Within-run imprecision: ranged from 5.1 % CV to 9.6% CV for concentrations from approximately 18 to 513 U/mL. |
| Between-run imprecision: ranged from 3.1% CV to 5.8% CV. | ||
| Total imprecision: ranged from 7.7% CV to 10.8% CV. |
Assessment of Imprecision Performance:
The reported total imprecision (7.7% - 10.8% CV) falls largely within the acceptance criteria of ≤ 10% for concentrations between 15 and 500 U/mL.
The statement "Total imprecision ranged from 7.7% CV to 10.8% CV" suggests that within the tested range (18 to 513 U/mL), there might be some values slightly exceeding 10% CV, likely towards the upper end of the 500 U/mL range or slightly above it. The acceptance criteria for concentrations greater than 500 U/mL is ≤ 12%. The summary states that "Imprecision above 500 U/mL was the only performance characteristic revised," implying the device does meet the ≤ 12% criterion for concentrations > 500 U/mL, even if not explicitly detailed in the reported values. The overall conclusion states that the modification to imprecision above 500 U/mL "was not found to impact the safety and efficacy of the device."
2. Sample size used for the test set and the data provenance
The document provides a "Summary of Precision Study" which states:
- Within-run assay imprecision was tested for concentrations from approximately 18 to 513 U/mL.
- Data Provenance: Not explicitly stated, but clinical precision studies for diagnostic devices are typically conducted in a controlled laboratory setting (e.g., in-house or contract research organization). It's reasonable to infer this was a prospective study designed to assess the performance of the modified device. The country of origin is not specified.
The exact number of samples (individual patient samples or spiked control samples) used to generate these imprecision ranges is not provided. Usually, imprecision studies involve running multiple replicates of control samples at different concentrations across various runs and days.
3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts
Not applicable. This is an in-vitro diagnostic (IVD) device for quantitative antigen determination, not a device requiring human expert interpretation of images or other subjective data for ground truth establishment. The "ground truth" for precision studies relies on the known or reference values of the control materials used.
4. Adjudication method for the test set
Not applicable. As described above, this is an IVD device for quantitative measurement. There is no subjective interpretation requiring adjudication among experts.
5. If a multi reader multi case (MRMC) comparative effectiveness study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance
Not applicable. This device is an IVD immunoassay, not an AI-assisted diagnostic tool requiring human reader studies or MRMC analyses.
6. If a standalone (i.e. algorithm only without human-in-the loop performance) was done
Yes, the precision study evaluates the performance of the Access® BR Monitor assay as a standalone algorithm/device. The results (CV percentages) reflect the inherent performance of the instrument and reagents in measuring CA 15-3 antigen levels without human subjective interpretation.
7. The type of ground truth used
The ground truth for the imprecision study is based on the known or reference concentrations of the control samples used. These control samples are typically manufactured to contain specific, verified concentrations of the CA 15-3 antigen.
8. The sample size for the training set
Not applicable. This is not a machine learning or AI-based device that requires a distinct "training set" in the conventional sense. The device's operational parameters (e.g., reagent formulation, calibration curves) are established through manufacturing and assay development processes, not through a 'training set' of data in the AI context.
9. How the ground truth for the training set was established
Not applicable, as explained in point 8. The "ground truth" for establishing the assay's operational characteristics would stem from analytical characterization during development, using reference materials and established analytical methods.
§ 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.