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. The CellTracks Analyzer II is for analysis of rare cells that are isolated from biological samples. 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 and specific reagent kits that contain a ferrofluid-based capture reagent and fluorescent reagents 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 immunomagnetic 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.

AI/ML Overview

Here's an analysis of the acceptance criteria and the study proving the device meets them, based on the provided text:

Acceptance Criteria and Device Performance

The document doesn't explicitly state pre-defined "acceptance criteria" in a structured list with target values. Instead, it demonstrates substantial equivalence to a predicate device by showing high correlation and comparable performance in several metrics. For this analysis, I will infer the implicit acceptance criteria from the reported findings, primarily focusing on correlation with the predicate device and the specified performance characteristics.

Acceptance Criteria Category (Inferred)	Specific Metric	Target	Reported Device Performance	Meets Criteria?
Correlation with Predicate Device (Clinical Samples)	Pearson's Correlation Coefficient (for ≥1.5 CTCs)	> 0.95 (implied by 0.9996 results)	0.9996	Yes
	Linear Regression Slope (for ≥1.5 CTCs)	Close to 1 (implied by 1.136 results, discussed)	1.136	Yes (with discussion)
	r² value (for ≥1.5 CTCs)	Close to 1 (implied by 0.9992 results)	0.9992	Yes
Correlation with Predicate Device (Spiked Cell-Line Samples)	r-value for MCF-7 cells	≥ 0.98 (explicitly stated in conclusion)	0.994	Yes
	r-value for SKBr-3 cells	≥ 0.98 (explicitly stated in conclusion)	0.984	Yes
	r-value for PC3-9 cells	≥ 0.98 (explicitly stated in conclusion)	0.963	No (but combined analysis brings it up)
	r-value for all 3 cell lines combined	≥ 0.98 (explicitly stated in conclusion)	0.966	No (but combined analysis brings it up)
	Correction: The document states "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." This appears to be a misstatement or a reinterpretation of their own result (0.966 is not "at least 0.98"). However, the individual r-values for cell lines are high. The overall conclusion states "very high degree of correlation." Given the context of substantial equivalence, the inference is that a high correlation, near 1, is the goal.
Linearity	Regression slope (expected vs. observed)	Close to 1 (e.g., 0.95-1.05)	1.007	Yes
	r² value	Close to 1 (e.g.,>0.99)	0.99	Yes
	Reportable Range	Comparable to predicate (4-1022 CTCs)	0-1238 cells/ul	Yes (broader range covered)
Precision	Coefficient of Variation (CV) for Low Control (average 48 cells)	Comparable to predicate (15.8%)	18%	Yes (stated as comparable)
	Coefficient of Variation (CV) for High Control (average 969 cells)	Comparable to predicate (9.4%)	5%	Yes (stated as comparable)

Note on "Meets Criteria?": The document focuses on demonstrating substantial equivalence to the predicate device. Therefore, "meets criteria" implies that the new device's performance is comparable to or better than the predicate's, and the statistical metrics (correlation coefficients, slopes, r-values) indicate a very strong agreement between the two systems. While some individual r-values or slopes might not perfectly match '1' or '0.98', the overall conclusion consistently asserts comparability and high correlation. The intercept values were also deemed "not statistically different than 0."

Study Details

Sample sizes used for the test set and data provenance:
- Clinical Samples Study: 83 specimens with an average of ≥ 1.5 circulating tumor cells. Samples were obtained from thirteen geographically dispersed sites. Based on the mention of "cancer patients," this data is retrospective and of clinical origin. The country of origin is not specified but implied to be the US given the FDA submission.
- Spiked Cell-Line Samples Study: 45 samples were analyzed on each of the two platforms (CellTracks Analyzer II and CellSpotter Analyzer). These were normal donor whole blood samples spiked with tissue culture cell lines (SKBr-3, PC3-9, and MCF-7) at three different levels (~5, ~50, and ~1000 cells). This is a prospective, controlled laboratory study.
Number of experts used to establish the ground truth for the test set and the qualifications of those experts:
- The document does not specify the number of experts or their qualifications for establishing ground truth for the clinical or spiked samples.
- For the clinical samples, "analysis was performed by Medical Technologists." This refers to the operators of the devices, not necessarily experts establishing a separate ground truth.
- For the spiked samples, the "ground truth" is defined by the known number of cells spiked into the normal donor blood.
Adjudication method for the test set:
- The document does not mention an adjudication method for the test set. For the clinical samples, it's implied that the device outputs were compared to each other. For spiked samples, it's a comparison to the known spiked quantity.
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:
- No MRMC comparative effectiveness study was done as described. This study is a device-to-device comparison, not an assessment of human reader performance with or without AI assistance. The device is a semi-automated fluorescence microscope where a user classifies cells; however, the study design does not directly evaluate the impact on human reader performance, but rather the performance consistency between the new and predicate device.
If a standalone (i.e. algorithm only without human-in-the-loop performance) was done:
- The device, CellTracks Analyzer II, is described as a "semi-automated fluorescence microscope" where "Cell images from the filter are compiled and presented in a gallery format for final cell classification by the user." This indicates it's fundamentally a human-in-the-loop system. Therefore, a standalone (algorithm only) performance study, without human classification, was not performed nor would it be relevant for this device's intended use according to its description. The studies performed compare the system's output (which includes the final user classification) between the new and predicate device.
The type of ground truth used:
- Clinical Samples: The ground truth for this comparison study was the predicate device's output (CellSpotter predicate device), as the study compared the CellTracks Analyzer II to the CellSpotter predicate device using clinical samples.
- Spiked Cell-Line Samples: The ground truth was the known spiked quantity of cells. This is a form of engineered or "gold standard" ground truth.
- Linearity & Precision Studies: The ground truth for linearity was the known dilution of cells. For precision, it was the known fixed, pre-stained cells in the control kit.
The sample size for the training set:
- The document does not mention a "training set" in the context of machine learning or AI. The studies performed are verification and validation studies for hardware and integrated system performance against a predicate device or known inputs.
How the ground truth for the training set was established:
- As there's no mention of a "training set" in the AI/ML sense, this question is not applicable. The device appears to be an optical detection and enumeration system, not an AI/ML-driven classifier that requires a training set. The "software" mentioned likely refers to control and visualization software, not a self-learning algorithm.

Summary

{0}------------------------------------------------

MAR 1 5 2005

K050145

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

Device description

{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:

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 ____________________________________________________________________________________________________________________________________________________________________

Regulation Number and Section

§ 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.