← Product Code [NRS](/submissions/HE/subpart-i%E2%80%94hematology-reagents/NRS) · K040898

# CELLSEARCH EPITHELIAL CELL CONTROL KIT (K040898)

_Veridex, LLC · NRS · Jun 28, 2004 · Hematology · SESE_

**Canonical URL:** https://fda.innolitics.com/submissions/HE/subpart-i%E2%80%94hematology-reagents/NRS/K040898

## Device Facts

- **Applicant:** Veridex, LLC
- **Product Code:** [NRS](/submissions/HE/subpart-i%E2%80%94hematology-reagents/NRS.md)
- **Decision Date:** Jun 28, 2004
- **Decision:** SESE
- **Submission Type:** Traditional
- **Regulation:** 21 CFR 864.8625
- **Device Class:** Class 2
- **Review Panel:** Hematology

## Indications for Use

The CellSearch™ Epithelial Cell Control kit is intended for use as an assayed control, when performing the CellSearch™ Epithelial Cell Kit on the CellTracks® AutoPrep System, to ensure that the sample detection and identification systems are working. For in vitro diagnostic use.

## Device Story

Control kit containing fixed SKBR-3 breast carcinoma cells; two populations (high/low concentration) distinguished by specific fluorescent dyes (DiOC16(3) and DiIC18(5)). Used as substitute for patient sample to verify CellSearch™ assay performance; processed via CellTracks® AutoPrep System; analyzed by CellSpotter® Analyzer. System automatically identifies control cells as circulating tumor cells (CTCs) via magnetic capture and fluorescent imaging. Provides model system for healthcare providers to evaluate detection/identification system functionality; ensures assay reliability before patient sample analysis.

## Clinical Evidence

No clinical data. Bench testing only. Analytical performance included a 20-day precision study (NCCLS EP-5A) and a 39-day system performance verification across three sites/instruments. Total precision (%CV) for high control cells was 5% and low control cells was 15%. Matrix effects study compared control cells in product matrix versus whole blood; results showed high-end concentration difference was statistically significant (p=0.004) but clinically acceptable for control purposes.

## Technological Characteristics

Fixed SKBR-3 breast carcinoma cells in matrix (Histopaque 1083, 5% BSA, 0.1% sodium azide). Single-use vials. Fluorescently labeled (DiOC16(3) and DiIC18(5)). Operates with CellTracks® AutoPrep System and CellSpotter® Analyzer. Magnetic capture and fluorescent imaging principle. Shelf life 9 months at 4°C.

## Regulatory Identification

A hematology quality control mixture is a device used to ascertain the accuracy and precision of manual, semiautomated, and automated determinations of cell parameters such as white cell count (WBC), red cell count (RBC), platelet count (PLT), hemoglobin, hematocrit (HCT), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), and mean corpuscular hemoglobin concentration (MCHC).

## Special Controls

*Classification.* Class II (special controls). Except when intended for use in blood components, the device is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 864.9.

## Predicate Devices

- Control Cell Kit ([K031588](/device/K031588.md))

## Submission Summary (Full Text)

> This content was OCRed from public FDA records by [Innolitics](https://innolitics.com). If you use, quote, summarize, crawl, or train on this content, cite Innolitics at https://innolitics.com.
>
> Innolitics is a medical-device software consultancy. We help companies design, build, and clear FDA-regulated software and AI/ML devices, including [a 510(k)](https://innolitics.com/services/510ks/), [a De Novo](https://innolitics.com/services/regulatory/), [a SaMD](https://innolitics.com/services/end-to-end-samd/), [an AI/ML medical device](https://innolitics.com/services/medical-imaging-ai-development/), or [an FDA regulatory strategy](https://innolitics.com/services/regulatory/).

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# 510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY DEVICE ONLY TEMPLATE

A. 510(k) Number:
K040898

B. Purpose for Submission:
New device

C. Analyte:
Circulating Breast Epithelial Tumor Cells

D. Type of Test:
Quality Control Material

E. Applicant:
Veridex, LLC (Johnson and Johnson Company)

F. Proprietary and Established Names:
CellSearch™ Epithelial Cell Control Kit

G. Regulatory Information:
1. Regulation section:
21 CFR 864.8625
2. Classification:
Class II
3. Product Code:
NRS
4. Panel:
Hematology Panel

H. Intended Use:
5. Intended use(s):
The CellSearch™ Epithelial Cell Control Kit is intended for use as an assay control to ensure that the sample detection and identification systems are working when performing the CellSearch™ Assay.
6. Indication(s) for use:
A CellSearch™ Epithelial Cell Control bottle is substituted for a patient sample to verify the performance of the CellSearch™ Epithelial Cell Kit reagents; sample processing by the CellTracks® AutoPrep System; and cell analysis by the CellSpotter® Analyzer.
7. Special condition for use statement(s):
For prescription use only
8. Special instrument Requirements:

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To be used with the CellTracks® AutoPrep System and the CellSpotter® Analyzer.

# I. Device Description:

The CellSearch Epithelial Cell Control Kit contains single-use vials of fixed cells from the breast carcinoma cell line SKBR-3. Each vial contains two populations of the SKBR-3 cells at different concentrations, low and high, which are distinguished from each other by use of fluorescent dyes that are specific for each population. Stability studies have been performed for shelf life; there is no need for open vial studies because the control is single use. The shelf-life is 9 months at  $4^{\mathrm{0}}\mathrm{C}$ .

# H. Substantial Equivalence Information:

1. Predicate device name(s): Control Cell Kit cleared with the CellSearch CellSpotter
2. Predicate K number(s): K031588
3. Comparison with predicate:

|  Similarities  |   |   |
| --- | --- | --- |
|  Item | Device | Predicate  |
|  Indications for Use | The CellSearch™ Epithelial Cell Control Kit is intended for use as an assayed control when running the CellSearch™ Epithelial Cell Kit on the CellSpotter® Analyzer/Cell Tracks® AutoPrep System to ensure the sample detection and identification systems are able to detect circulating tumor cells. | The Control Cell Kit is for use as an assay control when running the CellSearch™ assay to ensure that the sample detection and identification systems are working.  |
|  Cells | Breast Cancer Cell Line (SKBr-3) | Same  |
|  Fixative | Paraformaldehyde | Same  |
|  Dyes used to pre-label cells | DiOC16(3) for high control cell population. | Same  |
|  Control Matrix Ingredient | 5% Bovine Serum Albumin, 0.1% Sodium Azide | Same  |
|  Differences  |   |   |
|  Item | Device | Predicate  |
|  Control Matrix Ingredient | Histopaque 1083 | Phosphate Buffered Saline  |
|  Control Cell levels; Expected Target Values | Two populations of cells: High (1000 cells/test); Low (50 cells/test) | One population of cells: High (1000 cells/test)  |

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|  Dyes used to pre-label cells | DiIC18(5) for low control cell population | None  |
| --- | --- | --- |
|  Tests/vial | Unit dose ( one test/vial); 24 tests per kit | 10 tests/vial; 10 tests per kit  |
|  |   |   |

I. Standard/Guidance Document Referenced (if applicable):
- Guidance for FDA Reviewers and Industry for the Content of Premarket Submissions (draft:3 August 1999)
- In Vitro Diagnostic Devices: Guidance for the Preparation of 510(k) Submission (January 1997)
- Medical Devices-Risk Management Part 1: Application of Risk Analysis, International Standards Organization, ISO 14971-1:1998 (E)
- Guidance for Industry. Points to Consider Guidance Document on Assayed and Unassayed Quality Control Materials.
- Points to Consider for Hematology Quality Control Materials. September 30, 1997.

J. Test Principle:
Each single use vial in the CellSearch™ Epithelial Cell Control Kit contains two populations of SKBR-3 cells at different concentrations (low and high). The two cell populations are distinguished from each other by use of different fluorescent dyes that are specific for each population. This permits simultaneous enumeration of low and high control cells by the CellSpotter® Analyzer. The CellSearch™ Epithelial Cell Control Kit with its pre-stained and fixed control cells are automatically identified as CTCs (circulating tumor cells) by the system. They are magnetically captured by the CellSpotter® Analyzer and acquired as images that are displayed to the user for final classification, thus providing a model system to evaluate the process.

Performance Characteristics (if/when applicable):

4. Analytical performance:
a. Precision/Reproducibility:
- A 20-day precision study was performed according to NCCLS EP-5A, Evaluation of Precision Performance of Clinical Chemistry Devices running duplicate control cell samples in the morning and afternoon each day at two sites. The total imprecision (%CV) for the High Control cells from Immunicon and an external site are 6.39 and 5.11 respectively. The acceptance range for these lot specific control cells was 939 to 1335 for the High Control and 22 to 81 for the Low Control. The count for both sites were within the acceptance ranges except for two tests where the High Control counts were below the acceptance number (2/80 = 2.5%). The reason for the outliers could not be determined, but they did not repeat.
- A system performance verification study was performed at three sites with three CellTrack® AutoPrep Systems and three CellSpotter® Analyzers, using two CellSearch™ Epithelial Control samples that were

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run per instrument twice a day over a 39-day period. The results of within-run and total precision standard deviation and  $\% \mathrm{CV}$  for each instrument, as well as combined are presented in the following table:

Estimates of Within-Run and Total Precision

|  AutoProp L.D. | # of Days | Estimate of Within-Run Precision |   |   |   | Estimate of Total Precision  |   |   |   |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
|   |   |  Std. Deviation |   | % CV |   | Std. Deviation |   | % CV  |   |
|   |   |  Low | High | Low | High | Low | High | Low | High  |
|  P1 | 24 | 7 | 51 | 14% | 5% | 7 | 50 | 15% | 4%  |
|  P2 | 24 | 8 | 57 | 17% | 5% | 7 | 57 | 15% | 5%  |
|  P3 | 24 | 9 | 55 | 17% | 5% | 8 | 61 | 16% | 5%  |
|  Overall | 60 | 8 | 54 | 16% | 5% | 8 | 56 | 15% | 5%  |

The range of recoveries for each instrument control cell runs is listed in the table below.

Range and Averages of Control Cell Recoveries

|  Control Cells Number | P1 Low | P2 High | P3 Low | P4 High | P5 Low | P6 High | Overall Low | High  |
| --- | --- | --- | --- | --- | --- | --- | --- | --- |
|  Maximum | 34 | 984 | 33 | 983 | 28 | 955 | 28 | 955  |
|  Maximum | 46 | 1224 | 68 | 1290 | 71 | 1261 | 71 | 1290  |
|  Average | 51 | 1103 | 49 | 1111 | 51 | 1125 | 50 | 1116  |

The average recoveries of the high and low control cells and CV of the duplicates are presented in the table below.

Average Recoveries and CV of the Low and High Control Cell Duplicates

|  AutoProp L.D. | # of Control Runs | Control #1 |   | Control #2 |   | All Control Runs |   |   |   | Overall Average %CV  |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
|   |   |  Average Results Low | High | Average Results Low | High | Average Results Low | High | No. Deviation Low | High  |   |
|  P1 | 48 | 22 | 108 | 49 | 110 | 33 | 112 | 3 | 48 | 15%  |
|  P2 | 48 | 48 | 118 | 58 | 104 | 49 | 111 | 7 | 44 | 15%  |
|  P3 | 48 | 58 | 124 | 52 | 120 | 53 | 125 | 7 | 44 | 15%  |
|  Overall | 128 | 58 | 117 | 58 | 118 | 55 | 118 | 6 | 43 | 15%  |

- A variability study with day-to-day; operator-to-operator; and instrument to instrument testing was performed. The study used three operators and three instruments over three days with two lots of control cells. The results are shown in the following tables.

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# Lot 1 Performance Summary Data

## A: High Control Cells

|  Operator | Instrument | Day 1 |   |   | Day 2 |   |   | Day 3 |   |   | Overall  |   |   |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
|   |   |  Ave. | S.D. | %CV | Ave. | S.D. | %CV | Ave. | S.D. | %CV | Ave. | S.D. | %CV  |
|  Oper#1 | P5 | 971 | 40 | 4.1 | 984 | 46 | 4.6 | 975 | 29 | 2.9 | 977 | 38 | 3.9  |
|  Oper#2 | E3 | 962 | 30 | 3.1 | 939 | 58 | 6.1 | 933 | 55 | 5.8 | 945 | 49 | 5.2  |
|  Oper#3 | E6 | 996 | 25 | 2.5 | 962 | 63 | 6.5 | 1010 | 47 | 4.6 | 989 | 50 | 5.0  |

## B: Low Control Cells

|  Operator | Instrument | Day 1 |   |   | Day 2 |   |   | Day 3 |   |   | Overall  |   |   |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
|   |   |  Ave. | S.D. | %CV | Ave. | S.D. | %CV | Ave. | S.D. | %CV | Ave. | S.D. | %CV  |
|  Oper#1 | P5 | 46 | 8 | 17.3 | 46 | 6 | 13.0 | 48 | 6 | 12.5 | 47 | 7 | 14.6  |
|  Oper#2 | E3 | 43 | 10 | 23.2 | 44 | 8 | 18.1 | 44 | 7 | 15.9 | 44 | 8 | 18.3  |
|  Oper#3 | E6 | 53 | 5 | 9.4 | 46 | 7 | 15.2 | 47 | 9 | 19.1 | 49 | 8 | 15.6  |

# Lot 2 Performance Summary Data

## A: High Control Cells

|  Operator | Instrument | Day 1 |   |   | Day 2 |   |   | Day 3 |   |   | Overall  |   |   |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
|   |   |  Ave. | S.D. | %CV | Ave. | S.D. | %CV | Ave. | S.D. | %CV | Ave. | S.D. | %CV  |
|  Oper#1 (CCR) | P9 | 1145 | 79 | 6.8 | 1134 | 40 | 3.5 | 1136 | 52 | 4.5 | 1139 | 57 | 5.0  |
|  Oper#2 LMW | P10 | 1184 | 27 | 2.2 | 1134 | 55 | 4.8 | 1158 | 54 | 4.6 | 1158 | 50 | 4.3  |
|  Oper#3 GM | E6 | 1153 | 60 | 5.2 | 1114 | 15 | 1.3 | 1086 | 15 | 1.3 | 1117 | 52 | 4.7  |

## B: Low Control Cells

|  Operator | Instrument | Day 1 |   |   | Day 2 |   |   | Day 3 |   |   | Overall  |   |   |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
|   |   |  Ave. | S.D. | %CV | Ave. | S.D. | %CV | Ave. | S.D. | %CV | Ave. | S.D. | %CV  |
|  Oper#1 (YY) | P5 | 51 | 7 | 13.7 | 50 | 8 | 16.0 | 51 | 6 | 11.7 | 51 | 7 | 13.4  |
|  Oper#2 MH | E3 | 50 | 7 | 14.0 | 56 | 11 | 19.6 | 50 | 8 | 16.0 | 52 | 9 | 17.5  |
|  Oper#3 CCR | E6 | 57 | 7 | 12.2 | 50 | 7 | 14.0 | 50 | 7 | 14.0 | 52 | 9 | 17.5  |

b. Linearity/assay reportable range:
Not applicable

c. Traceability (controls, calibrators, or method):
Not applicable.

d. Detection limit:
Not applicable.

e. Analytical specificity:
Not applicable

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f. Assay cut-off:
Not applicable

5. Comparison studies:
a. Method comparison with predicate device:
Not available

Matrix comparison:
The new Epithelial Cell Control is in a matrix consisting of Histopaque 1083; 5% Bovine Serum Albumin; and 0.1% sodium azide while the patient samples will be epithelial cells from whole blood. A matrix effects study was performed with the Control cells spiked into either the Control Cell Product Matrix or whole blood. Both samples were processed on the CellTrack® AutoPrep System and CellSpotter® Analyzer. The results indicate that at the low-end cell concentration, the means differed by only 1 cell between matrices and at the high-end cell concentration, the means differed by 67 cells; this difference for the high-end cell concentration is small but statistically significant. Data is in table below.

Results of Control Cells Spiked into Product Matrix or Whole Blood

|  Sample Number | Low Control Cell Population |   | High Control Cell Population  |   |
| --- | --- | --- | --- | --- |
|   |  Whole Blood | Control Cell Matrix | Whole Blood | Control Cell Matrix  |
|  1 | 67 | 43 | 740 | 754  |
|  2 | 47 | 43 | 809 | 802  |
|  3 | 36 | 30 | 763 | 799  |
|  4 | 35 | 42 | 767 | 873  |
|  5 | 41 | 46 | 754 | 887  |
|  6 | 35 | 33 | 808 | 849  |
|  7 | 42 | 56 | 775 | 885  |
|  8 | 34 | 37 | 763 | 866  |
|  Mean | 42 | 41 | 772 | 839  |
|  Std. Dev. | 11 | 8 | 25 | 49  |
|  % CV | 26.2% | 19.5% | 3.2% | 5.8%  |
|  t-test p-value | 0.859 |   | 0.004  |   |

3. Clinical studies:
a. Clinical sensitivity:
Not applicable
b. Clinical specificity:
Not applicable
c. Other clinical supportive data (when a and b are not applicable):
None provided

4. Clinical cut-off:
Not applicable.

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5. Expected values/Reference range: Not applicable

**Conclusion:**
The submitted information in this premarket notification is complete and supports a substantial equivalence decision.

---

**Source:** [https://fda.innolitics.com/submissions/HE/subpart-i%E2%80%94hematology-reagents/NRS/K040898](https://fda.innolitics.com/submissions/HE/subpart-i%E2%80%94hematology-reagents/NRS/K040898)

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