(148 days)
The CellSearch™ Circulating Tumor Cell Kit is intended for the enumeration of circulating tumor cells (CTC) of epithelial origin (CD45-, EpCAM+, and cytokeratins 8, 18+, and/or 19+) in whole blood.
The presence of CTC in the peripheral blood, as detected by the CellSearch™ Circulating Tumor Cell Kit, is associated with decreased progression free survival and decreased overall survival in patients treated for metastatic breast or metastatic colorectal cancer. The test is to be used as an aid in the monitoring of patients with metastatic breast or metastatic colorectal cancer. Serial testing for CTC should be used in conjunction with other clinical methods for monitoring breast and colorectal cancer. Evaluation of CTC at any time during the course of disease allows assessment of patient prognosis and is predictive of progression free survival and overall survival.
The CellSearch" Circulating Tumor Cell Kit contains a ferrofluid-based capture reagent and immunofluorescent reagents. The ferrofluid reagent consists of nanoparticles with a magnetic core surrounded by a polymeric layer coated with antibodies targeting the EpCAM antigen for capturing CTC. After immunomagnetic capture and enrichment, fluorescent reagents are added for identification and enumeration of CTC. The fluorescent reagents include the following: anti-CK-Phycoerythrin (PE) specific for the intracellular protein cytokeratin (characteristic of epithelial cells), DAPI which stains the cell nucleus, and anti-CD45-Allophycocyanin (APC) specific for leukocytes.
The reagent/sample mixture is dispensed by the CellTracks® AutoPrep® System into a cartridge that is inserted into a MagNest® cell presentation device. The strong magnetic field of the MagNest® device attracts the magnetically labeled epithelial cells to the surface of the cartridge. The CellTracks® Analyzer II or CellSpotter® Analyzer automatically scans the entire surface of the cartridge, acquires images and displays any event to the user where CK-PE and DAPI fluorescence are co-located. Images are presented to the user in a gallery format for final classification. An event is classified as a tumor cell when its morphological features are consistent with that of a tumor cell and it exhibits the phenotype EpCAM+, CK+, DAPI+ and CD45 -.
Here's a breakdown of the acceptance criteria and the study details for the CellSearch™ Circulating Tumor Cell Kit, based on the provided text:
1. Table of Acceptance Criteria and Reported Device Performance
The document describes several performance characteristics without explicitly stating "acceptance criteria" for each. However, the study results clearly demonstrate the device's performance in these areas.
| Performance Characteristic | Acceptance Criteria (Implicit) | Reported Device Performance |
|---|---|---|
| Recovery | High percentage of spiked tumor cells recovered. | 93% recovery on average over the tested CTC range (0-1300 cells). Specifically: |
- 1300 expected: 1215 mean observed (91-95% range)
- 325 expected: 308 mean observed (82-101% range)
- 81 expected: 85 mean observed (80-136% range)
- 20 expected: 22 mean observed (95-140% range)
- 5 expected: 7 mean observed (120-200% range)
Linear regression: Y=0.93x + 3.87, R=0.999. |
| Linearity/Reportable Range | Detection of CTCs should be linear over the reportable range. | Linear detection over the reportable range of 0 to 1238 tumor cells. After factoring out percent recovery, regression of observed vs. expected tumor cells yielded a slope of 1.007, an intercept of 3.0, and an R² = 0.990 (R = 0.995). |
| Limit of Detection (LoD) | Ability to detect a low number of CTCs. | 1 CTC per 7.5 mL can be detected by the CellTracks® Analyzer II. The 7% loss in recovery does not reduce this LoD. |
| System Reproducibility (Control) | Consistent results for control samples. | Low Control (N=99): Mean cell count 48, Total Precision Standard Deviation (% CV) 18%.
High Control (N=99): Mean cell count 969, Total Precision Standard Deviation (% CV) 5%. |
| System Reproducibility (Patient Samples - MBC) | Consistent results for duplicate patient samples for MBC. | MBC (N=163 duplicate samples): Regression equation Y=0.98x + 0.67, R=0.99. |
| System Reproducibility (Patient Samples - MCRC) | Consistent results for duplicate patient samples for MCRC. | MCRC (N=1627 duplicate samples): Regression equation Y=0.98x + 0.18, R²=0.96. |
| PFS Prediction (MCRC) | Ability to differentiate patient groups with significantly different Progression Free Survival based on CTC levels. | Baseline CTC: Median PFS significantly longer in
§ 866.6020 Immunomagnetic circulating cancer cell selection and enumeration system.
(a)
Identification. An immunomagnetic circulating cancer cell selection and enumeration system is a device that consists of biological probes, fluorochromes, and other reagents; preservation and preparation devices; and a semiautomated analytical instrument to select and count circulating cancer cells in a prepared sample of whole blood. This device is intended for adjunctive use in monitoring or predicting cancer disease progression, response to therapy, and for the detection of recurrent disease.(b)
Classification. Class II (special controls). The special control for this device is FDA's guidance document entitled “Class II Special Controls Guidance Document: Immunomagnetic Circulating Cancer Cell Selection and Enumeration System.” See § 866.1(e) for availability of this guidance document.