(50 days)
No
The device description and performance studies focus on semi-automated image analysis and user classification, with no mention of AI or ML algorithms for image processing or cell enumeration.
No.
Explanation: The device is described as an "in vitro diagnostic" tool used to "enumerate fluorescently labeled cells". It aids in the classification of cells for diagnostic purposes, rather than providing direct therapy.
Yes
The "Intended Use / Indications for Use" section explicitly states, "The system is for in vitro diagnostic use when used in tandem with specimen preparation equipment and reagents that are legally marketed for in vitro diagnostic use with this device."
No
The device description explicitly states that the product consists of the CellTracks® Analyzer II, which is a semi-automated fluorescence microscope, in addition to the dedicated computer and software. This indicates the device includes significant hardware components beyond just software.
Yes, this device is an IVD (In Vitro Diagnostic).
Here's why:
- Explicit Statement in Intended Use: The "Intended Use / Indications for Use" section clearly states: "The system is for in vitro diagnostic use when used in tandem with specimen preparation equipment and reagents that are legally marketed for in vitro diagnostic use with this device."
- Analysis of Biological Samples: The "Device Description" mentions that the device is for "analysis of rare cells that are isolated from biological samples." This is a key characteristic of IVD devices, which are used to examine specimens derived from the human body.
- Use with Specific Reagent Kits: The device is used in conjunction with "specific reagent kits that contain a ferrofluid-based capture reagent and fluorescent reagents for the detection and characterization of the captured cells." These reagents are used to prepare and analyze the biological samples, further indicating its IVD nature.
- Clinical Laboratory Setting: The "Intended User / Care Setting" includes "traditional Clinical laboratories," which are the primary settings for IVD testing.
- Performance Studies using Clinical Samples: The performance studies described utilize "whole blood samples collected in CellSave® preservative tubes from cancer patients" and "whole blood from normal donors spiked with tissue culture cells." These are clinical samples, consistent with the evaluation of an IVD device.
- Comparison to Predicate IVD Device: The "Predicate Device(s)" section lists the "Veridex LLC CellSearch™ Epithelial Cell kit/Cell Spotter Analyzer; K031588 CellSpotter® Analyzer," which is a known IVD device. Comparing a new device to a predicate IVD is a common regulatory pathway for IVD devices.
All of these points strongly support the classification of the Immunicon CellTracks Analyzer II as an In Vitro Diagnostic device.
N/A
Intended Use / Indications for Use
The Immunicon CellTracks Analyzer II is a semi-automated fluorescence microscope used to enumerate fluorescently labeled cells that are immuno-magnetically selected and aligned. The system is for in vitro diagnostic use when used in tandem with specimen preparation equipment and reagents that are legally marketed for in vitro diagnostic use with this device.
Product codes (comma separated list FDA assigned to the subject device)
NQI
Device Description
The CellTracks® Analyzer II is a semi-automated fluorescence microscope. The product consists of the CellTracks® Analyzer II, a dedicated computer loaded with CellTracks® software, monitor, keyboard and mouse.
The CellTracks Analyzer II is for analysis of rare cells that are isolated from biological The Cell Huelto I mar 2010 . It is used in conjunction with the CellTracks® AutoPrep System, which automates, standardizes and optimizes the sample preparation with specific reagent kits.
The CellTracks Analyzer II is used in conjunction with the CellTracks AutoPrep System Frie Centractic reagent kits that contain a ferrofluid-based capture reagent and and in The Calagabouts for the detection and characterization of the captured cells. The ferrofluid reagent consists of nano-particles with a magnetic core surrounded by a polymeric layer coated with antibodies targeting the cells of interest. After portunomagnetic capture and enrichment, fluorescent reagents are added for identification and enumeration of the target cells.
The processed 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 causes the magnetically-labeled target cells to move to the surface of the cartridge. The CellTracks Analyzer II scans the entire surface of the cartridge with a series of fluorescence filters that are defined for the assay. Cell images from the filter are compiled and presented in a gallery format for final cell classification by the user.
Mentions image processing
Cell images from the filter are compiled and presented in a gallery format for final cell classification by the user.
Mentions AI, DNN, or ML
Not Found
Input Imaging Modality
fluorescence microscope
Anatomical Site
Not Found
Indicated Patient Age Range
Not Found
Intended User / Care Setting
traditional Clinical laboratories and Research Institutions.
Description of the training set, sample size, data source, and annotation protocol
Not Found
Description of the test set, sample size, data source, and annotation protocol
Not Found
Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)
Comparison Study of New Version of Device to Predicate using Clinical Samples: A comparison study was performed using whole blood samples collected in CellSave® preservative tubes from cancer patients. The samples were obtained from thirteen geographically dispersed sites and analysis was performed by Medical Technologists. Sample size was 83 specimens. The Pearson's correlation coefficient for 83 specimens with an average of ≥ 1.5 circulating tumor cells was 0.9996 with a linear regression slope of 1.136 and an r2 of 0.9992.
Comparison Study of New Version of Device to Predicate using Tissue Cultured Cell-Line Samples: A study was performed using duplicate samples that were split between the CellTracks Analyzer II platform and the CellSpotter Analyzer platform. The study consisted of spiking normal donor whole blood samples with three different tissue culture lines (SKBr-3, PC3-9 and MCF-7) at three different levels (~5, ~50, and ~1000). A total of 45 samples were analyzed on each of the two platforms.
For MCF-7 cells the slope of the regression line = 1.03, an intercept of 1.5 and an r2 = 0.994. For SKBr-3 cells, the slope of the regression line = 1.01 with an intercept of 2.9 and an r2 = 0.984. For PC3-9 cells, the slope of the regression line = 1.19 with an intercept of 10.5 and an r = 0.963. Analysis of data from all 3 tumor cell lines combined shows a slope of the regression line = 1.09 with an intercept of 1.5 and an r- = 0.966.
This data demonstrates that the AutoPrep / CellTracks Analyzer II platform is substantially equivalent to the CellPrep / CellSpotter Analyzer platform for the capture and enumeration of tumor cells from whole blood. The r values of 0.994, 0.984 and 0.963 for each of the 3 cell lines tested and an r value of 0.966 for all values combined means that the AutoPrep / CellTracks Analyzer II platform and the CellPrep / CellSpotter Analyzer platform have a correlation coefficient (r) of at least 0.98. The intercepts of 1.5, 2.9 and 10.5 for each of the cell lines tested and an intercept of 1.5 for all values, are not statistically different than 0. The slopes of 1.03, 1.01 and 1.19 for each of the 3 cell lines tested and a slope of 1.09 for all values suggest that the AutoPrep / CellTracks Analyzer II platform may have an improved dynamic range compared to the CellPrep / CellSpotter Analyzer platform for tumor cell capture and enumeration.
EP9-A Comparison Study with SkBr-3 Tissue Culture Cells: A comparison was made of the performance of the CellTracks Analyzer II system for the detection of tumor cells from whole blood versus the CellSpotter® Analyzer (K031588). This method comparison was conducted in accordance with NCCLS EP9-A, Method Comparison and Bias Estimation Using Patient Samples, using whole blood from normal donors spiked with tissue culture cells (SKBr-3) at tumor cell counts that cover the clinical range. The range of tumor cells observed in this experiment was from 0 to 1960. Linear regression analysis showed the slope of the CellTracks analyzer II tumor cell count versus the CellSpotter analyzer cell count regression line = 1.03 with an intercept of -1.25 and an r2 = 0.9998.
Linearity: During preclinical testing the CellTracks Analyzer II demonstrated linearity from 0 to 1238 cells/ul. Regression of the expected versus observed turnor cell numbers (range of 0 - 1238) gave a slope of 1.007 and an r2 of 0.99. These results demonstrate that the CellSearch™ CTC kit/CellTracks® Analyzer II detected the number of tumor cells expected from the known dilution. They also agree with those obtained previously for the predicate system (K031588) with a slope of 0.994, intercept of 5.7 and r2 = 0.99 over a reportable range of 4 to 1022 CTCs.
Precision: A 33-day precision study was performed according to NCCLS Guideline EPS-A, Evaluation of Precision Performance of Clinical Chemistry Devices, using a CellTracks Analyzer II with the control preparation from the CellSearch Circulating Tumor Cell Control Kit which contained fixed, pre-stained cells at two different spike levels, high and low. The systems total precision was determined to have a coefficient of variation of 18% at the low control cell level (average of 48 cells per sample) and a coefficient of variation of 5% at the high control cell level (average of 969 cells per sample). The results of the system reproducibility with CellSearch™ Circulating Tumor Cell Controls for the CellSearch™ Circulating Tumor Cell Kit are comparable to the reproducibility results for the predicate, which had a Total % CV of 9.4% for the High Control Cell (Mean 258) and 15.8% for the Low Control Cell (Mean 47). The reproducibility of the CellSearch™ Circulating Turnor Cell Kit meets the performance specification and is substantially equivalent to that of the predicate system.
Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)
Not Found
Predicate Device(s): If the device was cleared using the 510(k) pathway, identify the Predicate Device(s) K/DEN number used to claim substantial equivalence and list them here in a comma separated list exactly as they appear in the text. List the primary predicate first in the list.
The predicate device is the Veridex LLC CellSearch™ Epithelial Cell kit/Cell Spotter Analyzer. K031588
Reference Device(s): Identify the Reference Device(s) K/DEN number and list them here in a comma separated list exactly as they appear in the text.
Not Found
Predetermined Change Control Plan (PCCP) - All Relevant Information for the subject device only (e.g. presence / absence, what scope was granted / cleared under the PCCP, any restrictions, etc).
Not Found
§ 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.
0
MAR 1 5 2005
510(k) Summary
Date prepared 3/08/05.
This 510(k) summary is being submitted in accordance with the requirements of 21 CFR 807.92 (c).
The assigned 510(k) number is K050145.
Submitter's name, address, contact
The submitter of this premarket notification is Immunicon Corporation, 3401 Masons Mill Road, Suite 100, Huntingdon Valley, PA 19006. The official correspondent is Peter J Scott, Vice President of Quality Assurance and Regulatory Affairs (215-830-0777, fax 215-830-0751).
Identification of the Device and Predicate
The subject of this summary of Safety and Effectiveness is the Immunicon CellTracks® Analyzer II. The predicate device is the Veridex LLC CellSearch™ Epithelial Cell kit/Cell Spotter Analyzer. The subject device, CellTracks Analyzer II, is intended for use in traditional Clinical laboratories and Research Institutions. The common and classification name for this instrument is an Immunomagnetic Circulating Cancer Cell Selection and Enumeration System.
Intended Use
The Immunicon CellTracks Analyzer II is a semi-automated fluorescence microscope used to enumerate fluorescently labeled cells that are immuno-magnetically selected and aligned. The system is for in vitro diagnostic use when used in tandem with specimen preparation equipment and reagents that are legally marketed for in vitro diagnostic use with this device.
Device description
The CellTracks® Analyzer II is a semi-automated fluorescence microscope. The product consists of the CellTracks® Analyzer II, a dedicated computer loaded with CellTracks® software, monitor, keyboard and mouse.
1
The CellTracks Analyzer II is for analysis of rare cells that are isolated from biological The Cell Huelto I mar 2010 . It is used in conjunction with the CellTracks® AutoPrep System, which automates, standardizes and optimizes the sample preparation with specific reagent kits.
The CellTracks Analyzer II is used in conjunction with the CellTracks AutoPrep System Frie Centractic reagent kits that contain a ferrofluid-based capture reagent and and in The Calagabouts for the detection and characterization of the captured cells. The ferrofluid reagent consists of nano-particles with a magnetic core surrounded by a polymeric layer coated with antibodies targeting the cells of interest. After portunomagnetic capture and enrichment, fluorescent reagents are added for identification and enumeration of the target cells.
The processed 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 causes the magnetically-labeled target cells to move to the surface of the cartridge. The CellTracks Analyzer II scans the entire surface of the cartridge with a series of fluorescence filters that are defined for the assay. Cell images from the filter are compiled and presented in a gallery format for final cell classification by the user.
Technical Characteristics Summary
Changes to the predicate device were made by the original manufacturer of the device, Immunicon corporation, to replace a camera that was no longer manufactured by the camera manufacturer and to place the fluorescent microscope, camera, sample handling mechanism (stage), mercury arc lamp and power supply within a single housing.
The CellTracks Analyzer II does not raise any new issues of safety or effectiveness. The intended use of the predicate device to this particular application is essentially the same.
Discussion of testing
Comparison Study of New Version of Device to Predicate using Clinical Samples
A comparison study was performed using whole blood samples collected in CellSave® preservative tubes from cancer patients to determine circulating cancer cell counts. The samples were obtained from thirteen geographically dispersed sites and analysis was performed by Medical Technologists. The study compared the CellTracks Analyzer II to the CellSpotter predicate device. The Pearson's correlation coefficient for 83 specimens with an average of ≥ 1.5 circulating tumor cells was 0.9996 with a linear regression slope of 1.136 and an r2 of 0.9992.
Section 2 Page 2 of 5
2
Comparison Study of New Version of Device to Predicate using Tissue Cultured Cell-Line Samples
In addition, a study was performed using duplicate samples that were split between the CellTracks Analyzer II platform and the CellSpotter Analyzer platform. The study consisted of spiking normal donor whole blood samples with three different tissue culture lines (SKBr-3, PC3-9 and MCF-7) at three different levels (~5, ~50, and ~1000). The design and execution of this study is consistent with the NCCLS guideline EP9-A. A total of 45 samples were analyzed on each of the two platforms
For MCF-7 cells the slope of the regression line = 1.03, an intercept of 1.5 and an r2 = 0.994. For SKBr-3 cells, the slope of the regression line = 1.01 with an intercept of 2.9 and an r2 = 0.984. For PC3-9 cells, the slope of the regression line = 1.19 with an intercept of 10.5 and an r = 0.963. Analysis of data from all 3 tumor cell lines combined shows a slope of the regression line = 1.09 with an intercept of 1.5 and an r- = 0.966.
This data demonstrates that the AutoPrep / CellTracks Analyzer II platform is substantially equivalent to the CellPrep / CellSpotter Analyzer platform for the capture and enumeration of tumor cells from whole blood. The r values of 0.994, 0.984 and 0.963 for each of the 3 cell lines tested and an r value of 0.966 for all values combined means that the AutoPrep / CellTracks Analyzer II platform and the CellPrep / CellSpotter Analyzer platform have a correlation coefficient (r) of at least 0.98. Therefore, there is a very high degree of correlation between the results of the two platforms. The intercepts of 1.5. 2.9 and 10.5 for each of the cell lines tested and an intercept of 1.5 for all values, are not statistically different than 0. The slopes of 1.03, 1.01 and 1.19 for each of the 3 cell lines tested and a slope of 1.09 for all values however, suggest that the AutoPrep / CellTracks Analyzer II platform may have an improved dynamic range as compared to the CellPrep / CellSpotter Analyzer platform for tumor cell capture and enumeration.
The slope of 1.19 for PC3-9 cells may be due to an improved dynamic range of the AutoPrep / CellTracks Analyzer II system resulting in a flattening out of the response curve at higher cell numbers. In other words, the recovery of CTC by the AutoPrep / CellTracks Analyzer II platform at high numbers of cells may be somewhat more sensitive than recovery by the CellPrep / CellSpotter platform, particularly with lower EpCAM antigen density cells as is the case with PC3-9 cells (Figure 1). This difference could also be attributable to increased reliability of the AutoPrep as compared to the CellPrep for sample preparation. Regardless of this potential difference however, there appears to be no difference between the AutoPrep / CellTracks Analyzer II platform and the CellPrep / CellSpotter platform at the medical decision level of 5-50 CTC's.
Section 2 Page 3 of 5
3
EP9-A Comparison Study with SkBr-3 Tissue Culture Cells
A comparison was made of the performance of the CellTracks Analyzer II system for the detection of tumor cells from whole blood versus the CellSpotter® Analyzer (K031588). This method comparison was conducted in accordance with NCCLS EP9-A, Method Comparison and Bias Estimation Using Patient Samples, using whole blood from normal donors spiked with tissue culture cells (SKBr-3) at tumor cell counts that cover the clinical range. The range of tumor cells observed in this experiment was from 0 to 1960. Linear regression analysis showed the slope of the CellTracks analyzer II tumor cell count versus the CellSpotter analyzer cell count regression line = 1.03 with an intercept of -1.25 and an r2 = 0.9998.
Preclinical Studies
Linearity
During preclinical testing the CellTracks Analyzer II demonstrated linearity from 0 to 1238 cells/ul. Regression of the expected versus observed turnor cell numbers (range of 0 - 1238) gave a slope of 1.007 and an r2 of 0.99.
These results demonstrate that the CellSearch™ CTC kit/CellTracks® Analyzer II detected the number of tumor cells expected from the known dilution. They also agree with those obtained previously for the predicate system (K031588) with a slope of 0.994, intercept of 5.7 and r2 = 0.99 over a reportable range of 4 to 1022 CTCs. The linearity and reportable range of the new device is very similar to that of the predicate over a greater range of CTCs.
Precision
A 33-day precision study was performed according to NCCLS Guideline EPS-A, Evaluation of Precision Performance of Clinical Chemistry Devices, using a CellTracks Analyzer II with the control preparation from the CellSearch Circulating Tumor Cell Control Kit which contained fixed, pre-stained cells at two different spike levels, high and low. The systems total precision was determined to have a coefficient of variation of 18% at the low control cell level (average of 48 cells per sample) and a coefficient of variation of 5% at the high control cell level (average of 969 cells per sample).
The results of the system reproducibility with CellSearch™ Circulating Tumor Cell Controls for the CellSearch™ Circulating Tumor Cell Kit are comparable to the reproducibility results for the predicate, which had a Total % CV of 9.4% for the High Control Cell (Mean 258) and 15.8% for the Low Control Cell (Mean 47). The reproducibility of the CellSearch™ Circulating Turnor Cell Kit meets the performance specification and is substantially equivalent to that of the predicate system.
Section 2 Page 4 of 5
4
Conclusion
The conclusion drawn from the these studies is that the CellTracks Analyzer II is as safe and effective as the predicate device. No new issues of safety or effectiveness have been raised.
Section 2 Page 5 of 5
5
DEPARTMENT OF HEALTH & HUMAN SERVICES
Image /page/5/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a stylized depiction of an eagle or bird-like figure with three curved lines representing its wings or body. The text "DEPARTMENT OF HEALTH & HUMAN SERVICES USA" is arranged in a circular fashion around the bird symbol.
Food and Drug Administration 2098 Gaither Road Rockville MD 20850
Mr. Peter J. Scott Vice President, Quality Assurance and Regulatory Affairs Immunicon Corporation 3401 Masons Mill Road Huntingdon Valley, Pennsylvania 19006
MAR 1 5 2005
K050145 Re:
Trade/Device Name: Immunicon CellTracks® Analyzer II Regulation Number: 21 CFR § 866.6020 Regulation Name: Immunomagnetic Circulating Cancer Cell Selection and Enumeration System Regulatory Class: II Product Code: NQI
Dated: January 21, 2005 Received: January 24, 2005
Dear Mr. Scott:
We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to eonimer to that have been reclassified in accordance with the provisions of the Federal Food, Drug, and Cosmetic Act (Act) that do not require approval of a premarket approval application (PMA). You may, therefore, market the device, subject to the general controls provisions of the Act. The r ou may, dierely, mains of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration.
If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to such additional controls. Existing major regulations affecting your device can be found in Title 21, Code of Federal Regulations (CFR), Parts 800 to 895. In addition, FDA may publish further announcements concerning your device in the Federal Register.
Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must or any with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Parts 801 and 809); and good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820). This letter will allow you to begin marketing your device as described in your Section 510(k) premarket notification. The FDA finding of substantial equivalence of your device to a legally marketed predicate device results in a classification for your device and thus, permits your device to proceed to the market.
6
Page 2 -
If you desire specific information about the application of labeling requirements to your device, or questions on the promotion and advertising of your device, please contact the Office of In Vitro Diagnostic Device Evaluation and Safety at (240) 276-0484. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR Part 807.97). You may obtain other general information on your responsibilities under the Act from the I ou may obtain of Schell Manufacturers, International and Consumer Assistance at its toll-free number (800) 638-2041 or (301) 443-6597 or at its Internet address http://www.fda.gov/cdrh/industry/support/index.html
Sincerely yours,
lobatz Beckerh
Robert L. Becker, Jr., MD, PA Director Division of Immunology and Hematology Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health
Enclosure
7
Indications for Use
510(k) Number (if known):_K050145
Device Name: Immunicon CellTracks® Analyzer II
Indications For Use:
The Immunicon CellTracks Analyzer II is a semi-automated fluorescence microscope used to enumerate fluorescently labeled cells that are immuno-magnetically selected and aligned. The system is for in vitro diagnostic use when used in tandem with specimen preparation equipment and reagents that are legally marketed for in vitro diagnostic use with this device.
Prescription Use X ___________________________________________________________________________________________________________________________________________________________
AND/OR
Over-The-Counter Use
(Part 21 CFR 801 Subpart D)
(21 CFR 801 Subpart C)
(PLEASE DO NOT WRITE BELOW THIS LINE-CONTINUE ON ANOTHER PAGE IF NEEDED)
Concurrence of CDRH, Office of Device Evaluation (ODE)
Theresa M. Chan
Division Sign-Off
Division Slan-C
510K
Office of In Vitro Dlagnostic Device Evaluation and Safety
Page 1 of ____________________________________________________________________________________________________________________________________________________________________