MODIFICATION TO CELLSEARCH CIRCULATING TUMOR CELL KIT by VERIDEX, LLC

The CellSearch™ Circulating Tumor Cell Kit is intended for the enumeration of circulating tumor cells (CTC) of epithelial origin (CD45-, EpCAM+ and cytokeratin 8 & 18+, and/or cytokeratin 19+) in whole blood in conjunction with the CellTracks® AutoPrep System, the CellSpotter® Analyzer or CellTracks® Analyzer II, and the CellSearch™ Circulating Tumor Cell Control Kit.

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 cancer. A CTC count of 5 or more per 7.5 mL of blood generally is predictive of shorter progression free survival and shorter overall survival.

Device Description

Not Found

AI/ML Overview

This document is a 510(k) clearance letter for the CellSearch™ Circulating Tumor Cell Kit, not a study report. Therefore, it does not contain the detailed acceptance criteria and study results in the format requested. The letter confirms that the FDA has found the device to be substantially equivalent to legally marketed predicate devices.

However, I can extract what is present related to device function and some context of a study that would have been submitted to the FDA for this clearance.

Missing Information: Most of the requested information regarding detailed acceptance criteria, sample sizes, ground truth establishment, expert qualifications, adjudication methods, and MRMC study details are not available within this document. This information would typically be found in the 510(k) submission itself, which is a much larger technical dossier.

Here's what can be gathered, with the understanding that key details are absent:

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

Acceptance Criteria: Not explicitly stated in the document. The clearance letter only states that the device is "substantially equivalent" to predicate devices for its intended use. This implies the device met certain performance criteria compared to the predicate, but these criteria are not itemized here.
Reported Device Performance: The document provides the intended use and clinical significance of the device's measurements, rather than raw performance metrics.

Acceptance Criteria (Implied)	Reported Device Performance (Clinical Significance)
(Not explicitly stated in this document, typically comparative to predicate device performance in accuracy, precision, reproducibility, etc.)	"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 cancer."
"A CTC count of 5 or more per 7.5 mL of blood generally is predictive of shorter progression free survival and shorter overall survival."

2. Sample size used for the test set and the data provenance (e.g., country of origin of the data, retrospective or prospective)

Sample Size: Not available in this document.
Data Provenance: Not available in this document.

3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts (e.g., radiologist with 10 years of experience)

Not available in this document. Since this is an assay for enumerating circulating tumor cells using technology like immunomagnetic separation and image analysis, the "ground truth" would likely involve methods beyond just human expert review, potentially including independent staining and manual counting by trained laboratory personnel.

4. Adjudication method (e.g., 2+1, 3+1, none) for the test set

Not available in this document.

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

This device is for automated enumeration of circulating tumor cells using an analyzer (CellSpotter® Analyzer or CellTracks® Analyzer II). While there's a human element in initiating the test and interpreting the clinical significance, it's primarily an automated system. An "MRMC study" in the traditional sense (improving human reader performance with AI) is unlikely to be directly applicable as the primary claim is the enumeration by the device. The "AI" would be embedded in the CellSpotter® Analyzer's image analysis algorithms. The document does not provide details on such a study or effect sizes.

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

Yes, the core claim is for the "CellSearch™ Circulating Tumor Cell Kit" used in conjunction with the "CellTracks® AutoPrep System, the CellSpotter® Analyzer or CellTracks® Analyzer II". This implies a standalone performance component of the automated system in enumerating CTCs. However, the exact performance metrics of this standalone component are not provided in this clearance letter. The indications for use describe the kit's function with the automated analyzers.

7. The type of ground truth used (expert concensus, pathology, outcomes data, etc)

The "Indications for Use" mentions the device "is associated with decreased progression free survival and decreased overall survival in patients treated for metastatic breast cancer." This suggests that clinical outcomes data (progression-free survival and overall survival) were used to establish the clinical utility and significance of the CTC counts provided by the device. The "ground truth" for enumerating CTCs would typically involve orthogonal methods like manual microscopy counts by trained cytotechnologists or other validated cell counting methods, though this is not explicitly stated.

8. The sample size for the training set

Not available in this document.

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

Not available in this document.

Summary

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Food and Drug Administration 2098 Gaither Road Rockville MD 20850

OCT 2 7 2005

Veridex, LLC. c/o Ms. Debra J. Rasmussen Worldwide Executive Director Regulatory and Quality Affairs 33 Technology Dr. Warren, NJ 07059

Re: K052191

Trade/Device Name: CellSearch™ Circulating Tumor Cell Kit (Epithelial) Regulation Number: 21 CFR 866.6020 Regulation Name: Immunomagnetic Circulating Cancer Cell Selection and Enumeration System Regulatory Class: Class II Product Code: NQI Dated: August 10, 2005 Received: August 11, 2005

Dear Ms Rasmussen:

We have reviewed your Section 510(k) premarket notification of intent to market the device wf nave reviewed your boom in the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate commerce ass succed in 28, 1976, the enactment date of the Medical Device Amendments, or to devices that prior with , 20, 1978, as cordance 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 either class II (Special Controls) or class III (PMA), it n your de fiel to such additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. In addition, FDA may publish further announcements concerning your device in the Eederal Register.

Please be advised that FDA's issuance of a substantial equivalence determination does not mean r reaso oc advised that 2 a received 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 Part 801); good manufacturing practice requirements as set forth in the quality idoceming (21 CFR Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

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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 legally prematies nedicate 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 Part 801), please contact the Office of Compliance at (240) 276-0131. 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 Division of Small Manufacturers, International and Consumer Assistance at its toll-free number (800) 638-2041 or (301) 443-6597 or at its Internet address

(201) 115 0977 6.da.gov/cdrh/dsma/dsmamain.html

Sincerely yours,

Robert Beckerh

Robert L. Becker, Jr., M.D., PhD 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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Veridex LLC CellSearch™ Circulating Tumor Cell Kit

Indications for Use

510(k) Number (if known): K052191

Device Name: CellSearch™ Circulating Tumor Cell Kit

Indications for Use:

Prescription Use ਮ (Part 21 CFR 801 Subpart D)

AND/OR

Over-The-Counter Use (21 CFR 807 Subpart C) -

(PLEASE DO NOT WRITE BELOW THIS LINE-CONTINUE ON ANOTHER PAGE IF NEEDED)

Concurrence of CDRH, Office of In Vitro Diagnostic Devices (OIVD)

Division Sign-Off

ffice of In Vitro Diagnostic Device valuation and Safety

000004

5100(k) K052/91

neral Background and Regulatory Forms Confidential

Section I

Page 4 of 7

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.