(76 days)
The Chiron Diagnostics ACS:Centaur BR assay is an in vitro diagnostic test for the quantitative serial determination of cancer antigen CA 27.29 in human serum using the Chiron Diagnostics ACS:Centaur" Automated Chemiluminescence System. The test is intended for use as an aid in monitoring patients previously treated for Stage Il or Stage III breast cancer. Serial testing for CA 27,25 in the serum of patients who are clinically free of disease should be used in conjunction with other clinical methods used for the early detection of cancer recurrence. The test is also intended for use as an aid in the management of breast cancer patients with metastatic disease by monitoring the progression or regression of disease in response to treatment.
The Chiron Diagnostics ACS:Centaur BR assay is a fully automated, competitive immunoassay using direct, chemiluminescent technology. The Lite Reagent is composed of a monoclonal mouse antibody specific for CA 27.29, labeled with acridinium ester. The antibody used in the assay, MAb B27,29, binds to a peptide epitope in the tandem repeat region of the MUC-1 gene product. The Solid Phase is composed of purified CA 27.29, which is covalently coupled to paramagnetic particles. After onboard pretreatment, the sample is incubated with both Lite Reagent and Solid Phase simultaneously for 7.5 minutes.
Here's an analysis of the provided text, focusing on acceptance criteria and the study proving device performance:
1. Table of Acceptance Criteria and Reported Device Performance
| Performance Metric | Acceptance Criteria (Implied) | Reported Device Performance |
|---|---|---|
| Analytical Sensitivity | Minimum detectable concentration for CA 27.29 | 3.5 U/mL |
| Accuracy (Correlation to Predicate) | Strong correlation to the predicate device (ACS:180 BR) | Correlation coefficient (r) = 0.99 |
| Measuring Range | Range for CA 27.29 concentrations | Up to 450 U/mL |
| Linearity/Relationship | Close to 1:1 relationship with predicate device | ACS:Centaur BR = 1.00 (ACS:180 BR) - 0.94 U/mL |
Note on Implied Acceptance Criteria: The document primarily provides performance data without explicitly stating pre-defined acceptance criteria. However, when evaluating substantial equivalence, the performance of the new device is compared to a legally marketed predicate device. Therefore, the "acceptance criteria" are implicitly that the new device's performance should be comparable to or better than the predicate's, and meet general expectations for a diagnostic assay. A correlation coefficient of 0.99 is generally considered excellent for method comparisons.
2. Sample Size and Data Provenance for the Test Set
- Sample Size for Test Set: 225 samples were used for the accuracy study comparing the ACS:Centaur BR to the predicate device.
- Data Provenance: Not explicitly stated. The document doesn't mention the country of origin of the data or whether it was retrospective or prospective.
3. Number of Experts and Qualifications for Ground Truth
- This information is not provided in the given text. The study described is a method comparison (accuracy) study against a predicate device, not a study where a ground truth needed to be established by experts for classification or diagnosis.
4. Adjudication Method for the Test Set
- None. Adjudication is typically used when multiple observers assess a case and their interpretations need to be reconciled to establish a single ground truth. In this method comparison study, the "ground truth" for the new device's accuracy is its agreement with the predicate device's measurements. There are no human readers or diagnostic interpretations described that would require adjudication.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
- No, an MRMC study was not done. The study described is an analytical performance study comparing a new immunoassay to a predicate immunoassay. It does not involve human readers interpreting results or assessing the impact of AI assistance.
6. Standalone (Algorithm Only) Performance Study
- Yes, this is an analogous standalone performance study. The ACS:Centaur BR Immunoassay is an in-vitro diagnostic device that provides a quantitative measurement. The "algorithm" here is the entire immunoassay system (reagents, analyzer, and analytical process). The "standalone" performance is measured by its analytical sensitivity, measuring range, and accuracy when compared to a reference method (the predicate device). It's operating without human intervention for the measurement itself, only for collecting and interpreting the results.
7. Type of Ground Truth Used
- The "ground truth" for the accuracy study was the measurements obtained from the predicate device, the ACS:180 BR Immunoassay. This is a form of reference method comparison, where a new method's results are compared against an already established and validated method.
8. Sample Size for the Training Set
- The document does not explicitly mention a "training set" in the context of machine learning or algorithm development. For an immunoassay, the "training" equivalent would be the development and optimization of the assay itself through various experiments. The reported data relates to the final, validated product's performance.
9. How Ground Truth for the Training Set Was Established
- As a training set is not explicitly mentioned in the context of this immunoassay's validation, this information is not applicable/provided. The development of an immunoassay involves optimizing reagents and reaction conditions, which is an iterative process, but not typically referred to as "establishing ground truth for a training set" in the same way it would be for a machine learning model.
§ 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.