TETRACHROME REAGENTS AND TETRACXP SYSTEM

K121445 · Beckman Coulter, Inc. · OYE · Jul 26, 2013 · Hematology

Device Facts

• Record ID: K121445
• Device Name: TETRACHROME REAGENTS AND TETRACXP SYSTEM
• Applicant: Beckman Coulter, Inc.
• Product Code: OYE · Hematology
• Decision Date: Jul 26, 2013
• Decision: SESE
• Submission Type: Special
• Regulation: 21 CFR 864.5220
• Device Class: Class 2

Intended Use

CYTO-STAT tetraCHROME CD45-FITC/CD4-RD1/CD8-ECD/CD3-PC5 and CYTO-STAT tetraCHROME CD45-FITC/CD56-RD1/CD19-ECD/CD3-PC5 Monoclonal Antibody Reagents are for use on the COULTER EPICS XL/XL-MCL and Cytomics FC 500 Flow Cytometers. The reagents may also be used with the tetraONE SYSTEM for COULTER EPICS XL/XL-MCL Flow Cytometers or with tetraCXP SYSTEM for Cytomics FC 500 Flow Cytometers. Used alone or in combination with the automated systems, the reagents are intended "For In Vitro Diagnostic Use" and allow simultaneous identification and enumeration of total CD3+, total CD4+, total CD8+, dual CD3+/CD4+, dual CD3+/CD8+ and/or total CD3+, CD19+ and CD3-/CD56+ lymphocyte percentages and absolute counts in whole blood by flow cytometry. The systems also provide the CD4/CD8 ratio when using CD45-FITC/CD4-RD1/CD8-ECD/CD3-PC5. The tetraCXP Software for Cytomics FC 500 flow cytometry systems, CYTO-STAT tetraCHROME CD45-FITC/CD4-RD1/CD8-ECD/CD3-PC5, and CYTO-STAT tetraCHROME CD45-FITC/CD56-RD1/CD19-ECD/CD3-PC5 Monoclonal Antibody Reagents combine four-color fluorescent monoclonal antibody reagents, quality control reagents, an optional absolute count reagent, and software for automated analysis of lymphocyte populations in whole blood using Cytomics FC 500 flow cytometry systems with CXP Software. The system with CYTO-STAT tetraCHROME CD45-FITC/CD4-RD1/CD8-ECD/CD3-PC5 is intended "For In Vitro Diagnostic Use" and allows simultaneous identification and enumeration of total CD3+, total CD4+, total CD8+, dual CD3+/CD4+ and dual CD3+/CD8+ T lymphocyte population percentages and absolute counts. The system also provides the CD4/CD8 ratio. The system with CYTO-STAT tetraCHROME CD45-FITC/CD56-RD1/CD19-ECD/CD3-PC5 is intended "For In Vitro Diagnostic Use" and allows simultaneous identification and enumeration of total CD3+ (T), CD19+ (B), and CD3-/CD56+ (NK) lymphocyte population percentages and absolute counts. This reagent reflects the distribution of the three major subsets comprising the lymphocyte population upon which other lymphocyte enumeration studies are based.

Device Story

System uses monoclonal antibody reagents labeled with fluorochromes to bind specific cell surface antigens on lymphocytes in whole blood. Samples are processed via flow cytometry; white cells analyzed using manual or automated gating. tetraCXP SYSTEM software automates cytometer standardization, compensation (via QuickCOMP 4 Cells), and analysis of lymphocyte populations. Output includes percentages and absolute counts of T, B, and NK cell subsets and CD4/CD8 ratios. Used in clinical laboratory settings by trained personnel to assist in immunological assessment. Benefits include standardized, automated enumeration of lymphocyte subsets, reducing manual variability.

Clinical Evidence

No clinical data; bench testing only. Verification and validation activities performed per design control requirements to support labeling modifications.

Technological Characteristics

Reagent system for flow cytometry. No changes to hardware, software, or reagent composition. Packaging and manufacturing processes remain identical to predicate. Design controls per 21 CFR 820.30.

Indications for Use

Indicated for in vitro diagnostic use in clinical laboratories to identify and enumerate lymphocyte subsets (T, B, and NK cells) and their percentages/absolute counts in whole blood samples using flow cytometry. Used for monitoring lymphocyte populations, including CD4/CD8 ratios.

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

• tetraCHROME Reagents (K030408)
• tetraCXP SYSTEM for Cytomics FC 500 Flow Cytometer with CXP Software (K030828)

Submission Summary (Full Text)

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K121445

Image /page/0/Picture/1 description: The image shows the logo for Beckman Coulter. The logo consists of a circular graphic on the left and the company name on the right. The circular graphic has two curved lines inside of it. The text "BECKMAN COULTER" is written in a bold, sans-serif font, with "BECKMAN" on top of "COULTER".

# JUL 2 6 2013

# Special 510(k) Summary for CYTO-STAT® tetraCHROME™ CD45-FITC/CD4-RD1/CD8-ECD/CD3-PC5, CYTO-STAT® tetraCHROME™ CD45-FITC/CD56-RD1/CD19-ECD/CD3-PC5, and tetraCXP SYSTEM for Cytomics FC 500 with CXP Software

#### 1.0 Submitted By:

Nancy Nadler Group Manager, Regulatory Affairs Beckman Coulter, Inc. 11800 SW 147" Avenue, M/C: 31-B06 Miami, Florida 33196-2500 Telephone: [phone] FAX: [phone]

#### 2.0 Date Submitted:

May 14th, 2012

#### Device Name and Classification 3.0

Proprietary Name:

CYTO-STAT® tetraCHROME™ CD45-FITC/CD4-RD1/CD8-ECD/CD3-PC5 CYTO-STAT® tetraCHROME™ CD45-FITC/CD56-RD1/CD19-ECD/CD3-PC5

Classification Number: 21 CFR § 864.5220 - Automated differential cell counter

Classification: Class II

Product Code: GKZ

Panel: Hematology

Proprietary Name:

tetraCXP SYSTEM for Cytomics FC 500 with CXP Software

Classification Number: 21 CFR § 864.5220 – Automated differential cell counter

Classification: Class II

Product Code: GKZ

Panel: Hematology

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#### 4.0 Predicate Devices:

| Predicate Device | 510(K)<br>Number | Date Cleared | Classification | 21 CFR | Product<br>Code |
|-------------------------------------------------------------------------------|------------------|--------------|----------------|----------|-----------------|
| tetraCHROME<br>Reagents | K030408 | 3/4/2003 | Class II | 864.5220 | GKZ |
| tetraCXP SYSTEM<br>for Cytomics FC 500<br>Flow Cytometer with<br>CXP Software | K030828 | 5/21/2003 | Class II | 864.5220 | GKZ |

The change in this Special 510(k) is to labeling claims for specimen and prepared sample stability. There are no formulation or process changes to the reagents and no hardware or software changes to the instrumentation as a result of this these changes.

#### ર્સ () Description:

# CYTO-STAT tetraCHROME CD45-FITC/CD4-RD1/CD8-ECD/CD3-PC5 Monoclonal Antibody Reagent

This monoclonal antibody reagent identifies a lymphocyte gate based on CD45 bright positive staining (vs. side scatter) and allows simultaneous identification and enumeration of total CD3+, total CD4+ total CD8+, dual-positive CD3+/CD4+ and dual-positive CD3+/CD8+ lymphocytes in whole blood by flow cytometry.

The reagent is comprised of four murine monoclonal antibodies. Each antibody is labeled with a different color fluorochrome.

The reagent is for use on the COULTER EPICS XL/XL-MCL and Cytomics FC 500 Flow Cytometers with a manual gating procedure provided in the reagent product labeling. The reagent may also be used with the automated algorithm gating provided by tetraONE SYSTEM for COULTER EPICS XL/XL-MCL Flow Cytometers or tetraCXP SYSTEM for Cytomics FC 500 Flow Cytometers.

# CYTO-STAT tetraCHROME CD45-FITC/CD56-RD1/CD19-ECD/CD3-PC5 Monoclonal Antibody Reagent

This monoclonal antibody reagent identifies a lymphocyte gate based on CD45 bright positive staining (vs. side scatter) and allows simultaneous identification and enumeration of total CD3+, CD19+ and CD3-/CD56+ lymphocytes in whole blood by flow cytometry.

The reagent is comprised of four murine monoclonal antibodies. Each antibody is labeled with a different color fluorochrome.

The reagent is for use on the COULTER EPICS XL/XL-MCL and Cytomics FC 500 Flow Cytometers with a manual gating procedure provided in the reagent product labeling. The reagent may also be used with the automated algorithm gating provided by tetraONE SYSTEM

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for COULTER EPICS XL/XL-MCL Flow Cytometers or tetraCXP SYSTEM for Cytomics FC 500 Flow Cytometers.

### tetraCXP SYSTEM

tetraCXP SYSTEM for the Cytomics FC 500 with CXP Software consists of tetraCXP SYSTEM application software, tetraCHROME monoclonal antibody reagents, quality control reagents, an optional absolute count reagent, and automated software on the Cytomics FC 500 Flow Cytometer.

The system with CYTO-STAT tetraCHROME CD45-FITC/CD4-RD1/CD8-ECD/CD3-PC5 allows for simultaneous identification and cnumeration of total CD3+, total CD4+, total CD8+, dual CD3+/CD4+ and dual CD3+/CD8+ T lymphocyte population percentages and absolute counts. The system also provides the CD4/CD8 ratio.

The system with CYTO-STAT tetraCHROME CD45-FITC/CD56-RD1/CD19-ECD/CD3-PC5 is intended "For In Vitro Diagnostic Use" and allows simultaneous identification and enumeration of total CD3+ (T), CD19+ (B), and CD3-/CD56+ (NK) lymphocyte population percentages and absolute counts.

The tetraCXP SYSTEM Software comprises two functions: an Auto-Set Panel and an Automated Analysis Algorithm. The Auto-Set Panel automatically standardizes the cytometer, adjusts compensation settings, passes cytometer settings to designated test protocols, and verifics cytometer setup and antibody performance. Compensation settings are determined using QuickCOMP 4 Cells. The Automated Analysis Algorithm works in conjunction with the tetraCHROME monoclonal antibodies to automatically identify and enumerate sample populations

### Principle of Method

The Principal of Method for this test depends upon the ability of a monoclonal antibody to bind to the surface of cells expressing discrete antigenic determinants. Specific cell staining is accomplished by incubating whole blood with monoclonal antibody reagents. The CYTO-STAT tetraCHROME CD45-FITC/CD4-RD1/CD8-ECD/CD3-PC5 and CYTO-STAT tetraCHROME CD45-FITC/CD56-RD1/CD19-ECD/CD3-PC5 Monoclonal Antibody Reagents arc cach a combination of four murine monoclonal antibodics, each conjugated to a specific fluorochrome and specific for different cell surface antigens. Red blood cells are then lysed and the remaining white cells are analyzed on the flow cytometer with either manual gating or automated algorithm gating.

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#### Intended Use: 6.0

## tetraCHROME Reagents:

CYTO-STAT tetraCHROME CD45-FITC/CD4-RD1/CD8-ECD/CD3-PC5 and CYTO-STAT tetraCHROME CD45-FITC/CD56-RD1/CD19-ECD/CD3-PC5 Monoclonal Antibody Reagents are for use on the COULTER EPICS XL/XL-MCL and Cytomics FC 500 Flow Cytometers. The reagents may also be used with the tetraONE SYSTEM for COULTER EPICS XL/XL-MCL Flow Cytometers or with tetraCXP SYSTEM for Cytomics FC 500 Flow Cytometers.

Used alone or in combination with the automated systems, the reagents are intended "For In Vitro Diagnostic Use" and allow simultaneous identification and enumeration of total CD3+, total CD4+, total CD8+, dual CD3+/CD4+, dual CD3+/CD8+ and/or total CD3+, CD19+ and CD3-/CD56+ lymphocyte percentages and absolute counts in whole blood by flow cytomerry. The systems also provide the CD4/CD8 ratio when using CD45-FITC/CD4-RD1/CD8-ECD/CD3-PC5.

### tetraCXP SYSTEM:

The tetraCXP Software for Cytomics FC 500 flow cytometry systems, CYTO-STAT tetraCHROME CD45-FITC/CD4-RD1/CD8-ECD/CD3-PC5, and CYTO-STAT tetraCHROME CD45-FITC/CD56-RD1/CD19-ECD/CD3-PC5 Monoclonal Antibody Reagents combine fourcolor fluorescent monoclonal antibody reagents, quality control reagents, an optional absolute count reagent, and software for automated analysis of lymphocyte populations in whole blood using Cytomics FC 500 flow cytometry systems with CXP Software.

The system with CYTO-STAT tetraCHROME CD45-FITC/CD4-RD1/CD8-ECD/CD3-PC5 is intended "For In Vitro Diagnostic Use" and allows simultaneous identification and enumeration of total CD3+, total CD4+, total CD8+, dual CD3+/CD4+ and dual CD3+/CD8+ T lymphocyte population percentages and absolute counts. The system also provides the CD4/CD8 ratio.

The system with CYTO-STAT tetraCHROME CD45-FITC/CD56-RD1/CD19-ECD/CD3-PC5 is intended "For In Vitro Diagnostic Use" and allows simultaneous identification and enumeration of total CD3+ (T), CD19+ (B), and CD3-/CD56+ (NK) lymphocyte population percentages and absolute counts. This reagent reflects the distribution of the three major subsets comprising the Ivmphocvie population upon which other lymphocyte enumeration studies are based.

#### Comparison to Predicates: 7.0

The modified tetraCHROME reagents and tetraCXP SYSTEM have the following similarities to those which previously received 510(k) clearance:

- have the same fundamental indicated use, .
- use the same operating principle, .
- incorporate the same design (no changes to hardware, software or reagents), .
- incorporate the same materials, .
- have the same shelf life, and .
- are packaged using the same materials and processes. .

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The changes to these devices are limited to the claims made in the product labeling for specimen and prepared sample stability claims.

| Study | Study Design | Study Results |
|------------------------------------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|----------------------------------------------------------------------|
| Specimen and<br>prepared sample<br>stability studies | Specimens tested at various time<br>intervals to demonstrate sample and<br>prepared sample stability. Upper<br>limit of the drift is compared<br>against the acceptance limits. | Acceptable sample and prepared<br>sample stability results achieved. |

#### 8.0 Summary of Performance Data:

#### 9.0 Conclusion:

The data in the Premarket Notification on safety and effectiveness supports a finding that the modified tetraCXP SYSTEM, CYTO-STAT tetraCHROME CD45-FITC/CD4-RD1/CD8-ECD/CD3-PC5 and CYTO-STAT tetraCHROME CD45-FITC/CD56-RD1/CD19-ECD/CD3-PC5 Monoclonal Antibody Reagents are substantially equivalent to their respective predicate devices.

This summary of safety and effectiveness is being submitted in accordance with the requirements of the Safe Medical Device Act of 1990 and the implementing regulation 21 CFR 807.92.

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Image /page/5/Picture/0 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a circular seal with the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" arranged around the perimeter. Inside the circle is a stylized symbol featuring three abstract, wave-like shapes that resemble a person's profile.

DEPARTMENT OF HEALTH & HUMAN SERVICES

Public Health Service

Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-002

July 26, 2013

Beckman Coulter, Inc. C/O Nancy Nadler, Group Manager, Regulatory Affairs 11800 S.W. 147 Ave. MIS 31-B06 Miami, Florida 33196-2500

| Re: 510(k) Number: | k121445 |
|--------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Trade/Device Name: | CYTO-STAT® tetraCHROME™ CD45-FITC/CD4-RD 1/CD8-<br>ECD/CD3-PC5 Reagent CYTO-STAT® tetraCHROME™ CD45-<br>FITC/CD56-RD1/CD19-ECD/CD3-PC5 Reagent tetraCXP<br>SYSTEM for Cytomics FC 500 with CXP Software |
| Regulation Number: | 21 CFR 864.5220 |
| Regulation Name: | Automated differential cell counter. |
| Regulatory Class: | Class II |
| Product Code: | OYE |
| Dated: | July 5, 2013 |
| Received: | July 10, 2013 |

### Dear Ms. Nadler:

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. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.

If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to 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 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

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Page 2 - Ms. Nancy Nadler

CFR Part 807); labeling (21 CFR Part 801); medical device reporting (reporting of medical device-related adverse events) (21 CFR 803); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

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 Diagnostics and Radiological Health 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,

# Maria M. Chan -S

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

Enclosure

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# Indication for Use

# 510(k) Number (if known): K121445

# Device Name: CYTO-STAT® tetraCHROME™ CD45-FITC/CD4-RD1/CD8-ECD/CD3-PC5 CYTO-STAT® tetraCHROME™ CD45-FITC/CD56-RD1/CD19-ECD/CD3-PC5 tetraCXP SYSTEM for the Cytomics FC 500 with CXP Software

# Indication for Use:

# tetraCHROME Reagents:

CYTO-STAT tetraCHROME CD45-FITC/CD4-RD1/CD8-ECD/CD3-PC5 and CYTO-STAT tetraCHROME CD45-FITC/CD56-RD1/CD19-ECD/CD3-PC5 Monoclonal Antibody Reagents are for use on the COULTER EPICS XL/XL-MCL and Cytomics FC 500 Flow Cytometers. The reagents may also be used with the tetraONE SYSTEM for COULTER EPICS XL/XL-MCL Flow Cytometers or with tetraCXP SYSTEM for Cytomics FC 500 Flow Cytometers.

Used alone or in combination with the automated systems, the reagents are intended "For In Vitro Diagnostic Use" and allow simultaneous identification and enumeration of total CD3+, total CD4+, total CD8+, dual CD3+/CD4+, dual CD3+/CD8+ and/or total CD3+, CD19+ and CD3-/CD56+ lymphocyte percentages and absolute counts in whole blood by flow cytometry. The systems also provide the CD4/CD8 ratio when using CD45-FITC/CD4-RD1/CD8-ECD/CD3-PC5.

# tetraCXP SYSTEM:

The tetraCXP Software for Cytomics FC 500 flow cytometry systems, CYTO-STAT tetraCHROME CD45-FITC/CD4-RD1/CD8-ECD/CD3-PC5, and CYTO-STAT tetraCHROME CD45-FITC/CD56-RDI/CD19-ECD/CD3-PC5 Monoclonal Antibody Reagents combine four-color fluorescent monoclonal antibody reagents, quality control reagents, an optional absolute count reagent, and software for automated analysis of lymphocyte populations in whole blood using Cytomics FC 500 flow cytometry systems with CXP Software.

The system with CYTO-STAT tetraCHROME CD45-FITC/CD4-RD1/CD8-ECD/CD3-PC5 is intended "For In Vitro Diagnostic Use" and allows simultaneous identification and enumeration of total CD3+, total CD4+, total CD8+, dual CD3+/CD4+ and dual CD3+/CD8+ T lymphocyte population percentages and absolute counts. The system also provides the CD4/CD8 ratio.

The system with CYTO-STAT tetraCHROME CD45-FITC/CD56-RD1/CD19-ECD/CD3-PC5 is intended "For In Vitro Diagnostic Use" and allows simultaneous identification and enumeration of total CD3+ (T), CD19+(B), and CD3-/CD56+ (NK) lymphocyte population percentages and absolute counts. This reagent reflects the distribution of the three major subsets comprising the lymphocyte population upon which other lymphocyte enumeration studies are based.

tetraCHROME Reagents & tetraCXP SYSTEM 510(k) Submission Section 4: Indications for Use

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

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 Diagnostics and Radiological Health

Reena Philip -S

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

k121445 510(k)