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, colorectal or prostate* cancer. The test is to be used as an aid in the monitoring of patients with metastatic breast, colorectal or prostate cancer. Serial testing for CTC should be used in conjunction with other clinical methods for monitoring metastatic breast, colorectal and prostate 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.

*Metastatic prostate cancer patients in this study were defined as having two consecutive increases in the serum marker PSA above a reference level, despite standard hormonal management. These patients are commonly described as having androgen-independent, hormone-resistant, or castration-resistant prostate cancer.

Device Description

The CellSearch® Circulating Tumor Cell Kit contains a ferrofluid-based capture reagent and immunofluorescent reagents. The ferrofluid reagent consists of small particles 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-.

AI/ML Overview

The provided document (K103502) describes a 510(k) submission for a modified CellSearch® Circulating Tumor Cell Kit. However, it does not contain a study with acceptance criteria and a detailed report of device performance against those criteria in the way typically expected for a new or significantly modified device efficacy trial.

Instead, this 510(k) is a Special 510(k), which is submitted when there are minor changes to a legally marketed device that do not affect the intended use, fundamental scientific technology, mode of operation, or specimen type. In this particular case, the changes were labeling changes to assist the operator.

Therefore, the submission demonstrates equivalence to the predicate device (K073338) through verification of labeling specifications for the modified device and labeling process validation, rather than through a new clinical study with performance metrics against acceptance criteria.

Due to the nature of this particular 510(k) submission, many of the requested details about a clinical study, such as sample size, ground truth establishment for test and training sets, expert adjudication, and MRMC studies, are not present in the provided text.

Here's a breakdown of the available information:

1. A table of acceptance criteria and the reported device performance:

Acceptance Criteria	Reported Device Performance
Substantial Equivalence to Predicate Device (K073338)	Achieved through verification of labeling specifications for the modified device and labeling process validation. No change to intended use, fundamental scientific technology, mode of operations, or specimen type/identification.

2. Sample size used for the test set and the data provenance:

Not applicable / Not provided. The submission focused on equivalence based on labeling and process validation, not a new clinical performance study.

3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts:

Not applicable / Not provided. No new clinical test set requiring expert ground truth was described.

4. Adjudication method for the test set:

Not applicable / Not provided.

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:

No. This device is for circulating tumor cell enumeration, not an imaging device requiring human reader interpretation in the context of an MRMC study comparing AI assistance. The CellTracks Analyzer II® or CellSpotter® Analyzer presents images to the user for final classification, but the 510(k) does not detail MRMC studies for this specific change.

6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done:

Not explicitly stated as a new study for this 510(k). The device involves an automated process for capture, enrichment, and initial scanning, with a user performing final classification. The submission focuses on the impact of labeling changes, not on a standalone algorithm performance study.

7. The type of ground truth used:

Not applicable / Not provided for this specific 510(k). For the original predicate device, the "ground truth" for CTC identification would likely be based on the biological markers detected (EpCAM+, CK+, DAPI+, CD45-) and morphological features recognized by trained operators. However, this 510(k) does not present new performance data.

8. The sample size for the training set:

Not applicable / Not provided. No new algorithm training was described for this submission.

9. How the ground truth for the training set was established:

Not applicable / Not provided.

In summary: K103502 is a Special 510(k) for minor labeling changes to an already cleared device. It establishes substantial equivalence by demonstrating that these changes do not affect the device's fundamental performance, rather than by presenting new clinical performance data from a dedicated study with specific acceptance criteria and detailed methodologies for establishing ground truth, sample sizes, or reader studies. The "study" proving the device meets acceptance criteria in this context is the verification of labeling specifications and validation of the labeling process, demonstrating that the modified device remains functionally identical to the predicate.

Summary

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Summary Information

510(k) Summary

This summary of 510(k) safety and effectiveness information is being submitted in accordance with the requirements of SMDA 1990 and 21 CFR 807.92.

The assigned 510(k) number is: K/O3502

1. Submitter name, address, Veridex, LLC contact 1001 U.S. Route 202 Raritan, NJ 08869 Contact Person: Sarah McManus Date Special 510(k) prepared: 23 November 2010 2. Preparation Date Trade or Proprietary Name: CellSearch® Circulating Tumor Cell 3. Device name Kit Common Name: CellSearch® Circulating Tumor Cell Kit Classification Name: Immunomagnetic circulating cancer cell selection and enumeration system (21 CFR 866.6020, Product Code NQI) 4. Predicate device The predicate device is the CellSearch® Circulating Tumor Cell Kit (K073338, February 26, 2008)

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5. Device Description

Device intended use 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, colorectal or prostate* cancer. The test is to be used as an aid in the monitoring of patients with metastatic breast, colorectal or prostate cancer. Serial testing for CTC should be used in conjunction with other clinical methods for monitoring metastatic breast, colorectal and prostate 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.

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510(k) Summary, Continued

The CellSearch® Circulating Tumor Cell Kit (modified) is substantially equivalent to the CellSearch® Circulating Tumor Cell Kit (current - K073338: February 26, 2008). There has been no change to intended use, fundamental scientific technology, mode of operations, or specimen type/identification.

Changes from the predicate consist of labeling changes to assist the operator in identifying the presence and correct sequence of each reagent in the reagent tray.

The information presented in the premarket notification demonstrates that the performance of the CellSearch® Circulating Tumor Cell Kit (modified) is substantially equivalent to the predicate device.

Equivalence was demonstrated through verification of the labeling specifications for the modified device and labeling process validation.

The information presented in the premarket notification provides a reasonable assurance that the CellSearch® Circulating Tumor Cell Kit (modified) is safe and effective for the stated intended use.

7. Comparison to predicate device

8. Conclusions

CellSearch® Circulating Tumor Cell Kit 510(k) Summary Page 3 of 3

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Image /page/3/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a stylized caduceus symbol, which is a staff with two snakes coiled around it, positioned to the right. To the left of the caduceus, the text "DEPARTMENT OF HEALTH & HUMAN SERVICES • USA" is arranged in a circular fashion around the symbol. The text is in all caps and appears to be in a sans-serif font.

Food and Drug Administration 10903 New Hampshire Avenue Silver Spring, MD 20993

Veridex, LLC c/o Ms. Sarah McManus Manager, Regulatory Affairs 1001 US Hwy 202 North Raritan, NJ 08869

DEC 2 1 2010

Re: K103502

Trade/Device Name: CellSearch™ Circulating Tumor cell Kit Regulation Number: 21CFR§866.6020 Regulation Name: Immunomagnetic Circulating Cancer Cell Selection and Enumeration system Regulatory Class: Class II Product Code: NOI Dated: November 23, 2010 Received: November 29, 2010

Dear Ms. McManus

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 devices 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 general controls provisions 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 class II (Special Controls), 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 comply 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); medical device reporting (reporting of

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Page 2 -- Ms. Sarah McManus

medical device-related adverse events) (21 CFR 803); 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.

If you desire specific advice for your device on our labeling regulation (21 CFR Parts 801 and 809), please contact the Office of In Vitro Diagnostic Device Evaluation and Safety at (301) 796-5450. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to http://www.fda.gov/MedicalDevices/Safety/Reportal?roblem/default.htm for the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance.

You may obtain other general information on your responsibilities under the Act from the Division of Small Manufacturers, International and Consumer Assistance at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address http://www.fda.gov/cdrh/industry/support/index.html.

Sincerely yours,

Miriam Chan

Maria M. Chan, Ph.D Director Division of Immunology and Hematology Devices Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health

Enclosure

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Indications for Use

510(k) Number (if known):

103502

DEC. 21, 2010

Device Name: CellSearch® Circulating Tumor Cell Kit

Indication For Use:

Prescription Use X (21 CFR Part 801 Subpart D) And/Or

Over the Counter Use _ (21 CFR Part 801 Subpart C)

(Please DO NOT WRITE BELOW THIS LINE; CONTINUE ON ANOTHER PAGE IF NEEDED) Concurrence of CDRH, Office of In Vitro Diagnostic Device Evaluation and Safety (OIVD)

Reena Philip

Division Sign-Off Office of In Vitro Diagnostic Device Evaluation and Safety

510(k) K103502

Veridex, LLC

CellSearch® Circulating Tumor Cell Kit

Page 1 of 1

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.