THERMO SCIENTIFIC CYTO-CAL COUNT TUBES

K090810 · Microgenics Corp. · GKZ · Sep 18, 2009 · Hematology

Device Facts

• Record ID: K090810
• Device Name: THERMO SCIENTIFIC CYTO-CAL COUNT TUBES
• Applicant: Microgenics Corp.
• Product Code: GKZ · Hematology
• Decision Date: Sep 18, 2009
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 864.5220
• Device Class: Class 2

Intended Use

Thermo Scientific Cyto-Cal™ Count Tubes are used for determining absolute counts of leucocytes in blood. Thermo Scientific Cyto-Cal™ Count Tubes are used with the immunophenotyping reagents BD TriTEST™, flow cytometers BD FACS Calibur or BD FACS Canto, and software BD CellQuest or DIVA. Thermo Scientific Cyto-Cal™ Count Tubes can be used with the BD FACS™ Loader. This in vitro diagnostic device is intended for clinical use only.

Device Story

Thermo Scientific Cyto-Cal™ Count Tubes are single-use tubes containing a dried pellet of fluorescent microspheres (5.4 μm) with known concentration. Used in clinical laboratories with flow cytometers (BD FACS Calibur/Canto) and immunophenotyping reagents (BD TriTEST). Whole blood and antibody reagents are added directly to the tube; the pellet dissolves, releasing beads. During flow cytometric analysis, the device enables calculation of absolute cell counts (cells/μL) by comparing the number of positive cellular events to the number of fluorescent bead events. Data analysis is performed via software (e.g., BD MultiSET or BD CellQuest). The bead concentration serves as an internal reference to quantify lymphocyte subsets, aiding clinicians in immunophenotyping assessments.

Clinical Evidence

Bench testing only. Precision studies (n=21 runs per sample) showed CVs 4.7%-6.9%. Dilution recovery within ±10% of expected values. Method comparison (n=70 samples) against predicate showed correlation coefficient (R) > 0.99 for CD3+ and CD4+ counts. Carryover < 5%. Sample stability confirmed up to 72 hours (refrigerated blood) and 12 hours (labeled/lysed). External evaluation confirmed strong correlation across multiple cell types (CD3, CD4, CD8, CD16, CD19, CD56).

Technological Characteristics

Single-use tubes containing dried pellet of 5.4 µm fluorescent microspheres. Beads encapsulated with three dyes; emissions equivalent to FITC, PE, Per-CP, PE-Cy5, APC channels. Particle concentration ~50,000/tube. Compatible with flow cytometers (BD FACS Calibur/Canto). Storage 20-25 °C. Shelf-life 16+ months.

Indications for Use

Indicated for determining absolute leucocyte counts in blood samples for clinical immunophenotyping and immune response monitoring.

Regulatory Classification

Identification

An automated differential cell counter is a device used to identify one or more of the formed elements of the blood. The device may also have the capability to flag, count, or classify immature or abnormal hematopoietic cells of the blood, bone marrow, or other body fluids. These devices may combine an electronic particle counting method, optical method, or a flow cytometric method utilizing monoclonal CD (cluster designation) markers. The device includes accessory CD markers.

Special Controls

*Classification.* Class II (special controls). The special control for this device is the FDA document entitled “Class II Special Controls Guidance Document: Premarket Notifications for Automated Differential Cell Counters for Immature or Abnormal Blood Cells; Final Guidance for Industry and FDA.”

Predicate Devices

• BD Trucount Tubes (K965053)

Submission Summary (Full Text)

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## SEP 1 8 2009

## 510K SUMMARY

This summary of 510(k) safety and effectiveness information is being submitted in accordance with the requirements of Safe Medical Devices Act of 1990 and 21 CFR 807.92

The assigned 510(k) number is: K090810

## COMPANY/CONTACT PERSON

Lisa Charter

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Manager of Regulatory Affairs Microgenics Corporation Thermo Fisher Scientific, Clinical Diagnostics Division 46360 Fremont Blvd. Fremont, CA 94538 [phone] Office [phone] Fax Lisa. [e-mail]

## DATE PREPARED

August 30, 2009

#### DEVICE NAME

| Trade Name: | Thermo Scientific Cyto-Cal™ Count Tubes |
|------------------------|-----------------------------------------|
| Common Name: | Cyto-Cal™ Count Tubes |
| Device Classification: | Automated Differential Cell Counter |
| Regulation number: | 21 CFR 864.5220 |
| Product Code: | GKZ |

## INTENDED USE

Thermo Scientific Cyto-Cal™ Count Tubes are used for determining absolute counts of leucocytes in blood.

Thermo Scientific Cyto-Cal™ Count Tubes are used with the immunophenotyping reagents BD TriTEST™, flow cytometers BD FACS Calibur or BD FACS Canto, and software BD CellQuest or DIVA. Thermo Scientific Cyto-Cal[" Count Tubes can be used with the BD FACS™ Loader. This in vitro diagnostic device is intended for clinical use only.

#### SUBSTANȚIALLY EQUIVILANT PREDICATE DEVICE

Thermo Scientific Cyto-Cal™ Count Tubes are substantially equivalent to the previously cleared BD Trucount Tubes (K965053)

#### DESCRIPTION OF DEVICE

Thermo Scientific Cyto-Cal™ Count Tubes contain uniform 5.4 µm microspheres encapsulated with three dyes. The single tube contains fluorescent beads that have equivalent emissions to multiple channels for FITC. PE. Per-CP. PE-Cy5, APC. Each tube contains known number of fluorescent particles as indicated on the product label.

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## PRINCIPLES OF THE PROCEDURE

Procedures described herein apply to immunophenotyping of lymphocytes. In the procedure, the cell typing monoclonal antibody reagent and whole blood is added directly to the Cyto-Cal™ Count Tube. The dried pellet in the tube dissolves, releasing a known number of fluorescent beads. During analysis, the absolute number (cells/μL) of positive cells in the sample can be determined by comparing cellular events to bead events. If you are manually performing data analysis, simply divide the number of positive cellular events by the number of bead events, and then multiply by the Cyto-Cal Count bead concentration. The cell typing or immunophenotyping of lymphocytes is effectively used in monitoring immune response or in determining a particular cell count.

| Comparison | Predicate Device - BD Trucount Tubes | Thermo Scientific Cyto-Cal™ Count Tubes |
|----------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Intended Use | BD Trucount Tubes are used for determining absolute counts of leucocytes in blood. BD Trucount Tubes are designed for use with in vitro diagnostic products such as BD TriTEST™ reagents, and a suitably equipped flow cytometer. BD Trucount Tubes can be used with the BD FACS™ Loader. | Thermo Scientific Cyto-Cal™ Count Tubes are used for determining absolute counts of leucocytes in blood.<br>Thermo Scientific Cyto-Cal™ Count Tubes are used with the immunophenotyping reagents BD TriTEST™, flow cytometers BD FACS Calibur or BD FACS Canto, and software BD CellQuest or DIVA. Thermo Scientific Cyto-Cal™ Count Tubes can be used with the BD FACS™ Loader.<br>This in vitro diagnostic device is intended for clinical use only. |
| Test Principle | Add the cell typing monoclonal antibody reagent and whole blood directly to the BD Trucount Tubes. The lyophilized pellet in the tube dissolves, releasing a known number of fluorescent beads. During analysis, the absolute number (cells/µL) of positive cells in the sample can be determined by comparing cellular events to bead events. If the appropriate software, such as BD MultiSET™, is used, absolute counts will be determined by the software. If you are manually performing data analysis using software such as BD CellQuest™, simply divide the number of positive cellular events by the number of bead events, then multiply by the BD Trucount bead concentration. | Add the cell typing monoclonal antibody reagent and whole blood directly to the Thermo Scientific Cyto-Cal™ Count Tubes. The dried pellet in the tube dissolves, releasing a known number of fluorescent beads. During analysis, the absolute number (cells/µL) of positive cells in the sample can be determined by comparing cellular events to bead events. If the appropriate software, such as BD MultiSET™, is used, absolute counts will be determined by the software. If you are manually performing data analysis using software such as BD CellQuest™ divide the number of positive cellular events by the number of bead events, then multiply by the Thermo Scientific Cyto-Cal™ Count bead concentration. |

## COMPARISON OF TECHNOLOGICAL CHARACTERISTICS

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| Matrix | Freeze-dried pellet of fluorescent<br>beads in a single-use tube. | Dried pellet of fluorescent beads in<br>a single-use tube. |
|---------------------------|--------------------------------------------------------------------------|--------------------------------------------------------------------------------------------------|
| Reagents | Each pouch contains 25 BD<br>Trucount Tubes, sufficient for 25<br>tests. | Each package contains 25 Thermo<br>Scientific Cyto-Cal™ Count Tubes,<br>sufficient for 25 tests. |
| Instrument | Flow cytometer | Flow cytometer |
| Storage Condition | 2 to 25 °C | 20 to 25 °C |
| Particle<br>Concentration | ~50,000/tube | ~50,000/tube |
| Lysing reagent | FACSLyse | FACSLyse |

## SUMMARY OF CLINICAL TESTING

#### Precision

Three samples representing low, medium and high cell levels of CD3+ and CD4+ were used for these studies. Each sample was run 21 times to collect intra-assay precision data. The range of CVs for CD3+ cells, observed for all samples, was 4.9% (count of 3602 cells/μL) to 6.2% (count of 549 cells/μL). The range of CVs for CD4+ cells, observed for all samples, was 4.7% (count of 1996 cells/uL) to 6.9% (count of 369 cells/uL).

#### Dilution Recovery

Recovery was within +/_ 10% of expected value for levels tested from 0 to 1693 cells/pl. for CD3+CD4+ cells and 0 to 3923 cells/uL for CD3+ cells.

#### Method Comparison

We have selected a 70 samples for this study representing a wide range of results. For CD3+ the range is 1 cell / uL to 2463 cells / µL. For CD4+ the range is 0 cells / µL to 1947 cells / µL. There is strong correlation between Thermo Scientific Cyto-Cal™ Count Tubes and the predicate BD Trucount Tubes in all of these ranges. The correlation coefficient (R value) for both CD3+ and CD4+ to reference method is > than 0.99.

#### Carryover Study

Carry-over from a high cell count sample to a low cell count sample is less than 5%. :

#### Sample Stability

Cells count are within +/-10% of first test for up to 72 hours at 2 to 8 °C for blood samples, and for up to 12 hours at 2 to 8 ℃ for antibody labeled and lysed blood samples.

#### Reagent Shelf-Life Stabilities

Real time stability studies demonstrate the reagent is stable for at least 16 months at room temperature. Stability studies will continue for 24 months.

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## External Evaluation

The external site studies included a wide panel for fluorescent labeled monoclonal antibody (CD3, CD4, CD8, CD16, CD19, and CD56). The commonly used cell types including CD3+, CD4+, CD8+, CD16+CD56+, CD19+, and CD4/CD8 ratio are tabulated and compared to the reference BD Trucount method and Thermo Scientific Cyto-Cal™ Count Tubes method All of the method comparison results show a strong correlation between Thermo Scientific Cyto-Cal™ Count Tubes and the predicate BD Trucount Tubes in all of these cell types. The correlation coefficients (rvalue) meet the acceptance criteria.

#### CONCLUSION

As summarized, the Thermo Scientific Cyto-Cal™ Count Tubes are substantially equivalent to the BD Trucount Tubes. Substantial equivalence has been demonstrated through performance testing to verify that the device functions as intended and that design specifications have been satisfied.

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SEP 1 8 2009

Food and Drug Administration 10903 New Hampshire Avenue Document Mail Center - WO66-G609 Silver Spring, MD 20993-0002

Microgenics Corporation Thermo Fisher Scientific, Clinical Division c/o Lisa Charter Manager, Regulatory Affairs 46360 Fremont Boulevard Fremont, CA 94538

Re: k090810

Trade/Device Name: Thermo Scientific Cyto-Cal™ Count Tubes Regulation Number: 21 CFR 864.5220 Regulation Name: Differential Cell Counter Regulatory Class: Class II Product Code: GKZ Dated: September 2, 2009 Received: September 4, 2009

Dear Ms. Charter:

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. Iisting 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 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

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Page 2 - Ms. Lisa Charter

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 [phone]. 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/ReportaProblem/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 [phone] or [phone] or at its Internet address http://www.fda.gov/cdrh/industry/support/index.html.

Sincerely yours,

Marie M. Chan

Maria M. Chan, PhD Director Division of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health

Enclosure

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# Indication for Use

## 510(k) Number (if known): K090810

Device Name: Thermo Scientific Cyto-Cal™ Count Tubes

Indication For Use:

Thermo Scientific Cyto-Cal™ Count Tubes are used for determining absolute counts of leucocytes in blood.

Thermo Scientific Cyto-Cal™ Count Tubes are used with the immnuphenotyping reagents BD TriTEST™, flow cytometers BD FACS Calibur or BD FACS Canto, and software BD CellQuest or DIVA. Thermo Scientific Cyto-Cal™ Count Tubes can be used with the BD FACS™ Loader.

This in vitro diagnostic device is intended for clinical use only.

Prescription Use _ X

And/Or

Over the Counter Use

(21 CFR Part 801 Subpart D) Subpart C)

(21 CFR Part 801

(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)

Sunt K

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

510(k) K090810