CYTO-STAT tetraCHROME CD45-FITC/CD4-PE/CD8-ECD/CD3-PC5 Monoclonal antibody reagent is intended "For In Vitro Diagnostic Use", allowing the identification and enumeration of Total CD3+ (T cells), Total CD4+, Total CD8+, Dual CD3+/CD4+, Dual CD3+/CD8+ lymphocyte percentages and absolute counts as well as the CD4/CD8 ratio in whole blood flow cytometry. When used in conjunction with CD45-FITC/CD56-PE/CD19-ECD/CD3-PC5, the total lymphocyte percentage can be obtained. CD45-FITC/CD56-PE/CD19-ECD/CD3-PC5 monoclonal antibody reagent is intended "For In Vitro Diagnostic Use", allowing the identification and enumeration of total CD19+ (B cells) and CD3-/CD56+ (NK cells) lymphocyte percentages and absolute counts in whole blood flow cytometry. The total lymphocyte percentage can be obtained as well.

Device Description

The products are: The CYTO-STAT® tetraCHROME™ CD45-FITC/CD4-PE/CD8-ECD/CD3-PC5 Monoclonal Antibody Reagent and CYTO-STAT® tetraCHROME™ CD45-FITC/CD56-PE/CD19-ECD/CD3-PC5 Monoclonal Antibody Reagent. Each is a combination of four murine monoclonal antibodies, each conjugated to a different fluorochrome and specific for a different cell surface antigen.

AI/ML Overview

The provided document describes the "Summary of Safety and Effectiveness" for the CYTO-STAT® tetraCHROME™ CD45-FITC/CD4-PE/CD8-ECD/CD3-PC5 and CYTO-STAT® tetraCHROME™ CD45-FITC/CD56-PE/CD19-ECD/CD3-PC5 Monoclonal Antibody Reagents. This document is a 510(k) premarket notification for a medical device.

Crucially, this document specifies indications for use and details a device modification but it does not, in the provided text, describe specific acceptance criteria or a study proving the device meets those criteria with performance metrics, sample sizes, ground truth establishment, or expert adjudication as typically seen for AI/software devices.

The filing states that the device claims substantial equivalence to a previously cleared device (FDA 510(k) Number: K990172). This means that the review process focused on demonstrating that the modified device performs as safely and effectively as the predicate device, rather than establishing new performance benchmarks from scratch. The modification described is the use of the two monoclonal antibody reagent system components as stand-alone reagents on any equivalent flow cytometer system, allowing manual adjustment of parameters, as opposed to being solely part of the automated tetraONE System.

Therefore, many of the requested details about acceptance criteria, study design, and performance metrics are not typically included in a 510(k) summary for a substantial equivalence claim based on a modification of an existing device when no new clinical claims or significant technological changes are introduced that would necessitate new performance studies against specific acceptance thresholds.

Given the information provided, here's an attempt to answer the questions, highlighting what is present and what is absent:

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

The provided text does not explicitly state specific numerical acceptance criteria (e.g., sensitivity, specificity, accuracy thresholds) or present a table of reported device performance metrics against such criteria. The device is cleared based on demonstrating substantial equivalence to a predicate device for its intended use of identifying and enumerating lymphocyte subpopulations.

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

The document does not specify a sample size for a test set nor the data provenance (country of origin, retrospective/prospective). Substantial equivalence claims often rely on data from the predicate device or a limited bridge study.

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)

The document does not describe the use of experts to establish ground truth for a test set. This type of expert review is not typically part of a 510(k) submission for a diagnostic reagent claiming substantial equivalence, especially when the modification is primarily about device compatibility and manual operation. The "ground truth" for flow cytometry is generally established by established laboratory methods and controls.

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

The document does not mention any adjudication method for a test set.

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 MRMC comparative effectiveness study was done or is described. This device is a monoclonal antibody reagent for flow cytometry, not an AI or software-assisted diagnostic tool for "human readers" in the context of imaging interpretation. The modification allows for manual adjustment of parameters by an operator, which is the opposite of AI assistance.

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

This refers to a standalone performance of an algorithm. This device is not an algorithm. It is a reagent. While it can be used with automated flow cytometer systems that have software, the current filing is about its use as a stand-alone reagent on any equivalent flow cytometer system, allowing manual operation. Therefore, this question is not applicable in the context of this device.

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

The document does not explicitly describe the type of ground truth used in a formal study. For flow cytometry reagents, the "ground truth" is typically established through well-characterized cellular populations, internal and external controls, and comparisons to established reference methods for identifying specific cell markers. The document implies that the device's ability to identify and enumerate specific lymphocyte percentages and absolute counts is the performance metric, which would be compared against a reliable reference method if a new performance claim were being made. For this substantial equivalence claim, the predicate device's performance established the baseline.

8. The sample size for the training set

The document does not mention a "training set" as would be relevant for machine learning or AI models. This device is a diagnostic reagent.

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

As there is no mention of a training set, this question is not applicable.

In summary: The provided 510(k) summary is for a monoclonal antibody reagent. Its clearance is based on a claim of "substantial equivalence" to a previously marketed device (K990172) following a modification that allows its use as a standalone reagent on various flow cytometers with manual control. It is not an AI/software device, and therefore the types of studies, criteria, and methodologies typically required for AI/software, as implied by many of the questions, are not present in this regulatory document. The focus of such a submission is to demonstrate that the modified device is as safe and effective as the predicate device for its intended use, rather than presenting a de novo performance study against new, specific acceptance criteria.

Summary

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KO3O4O8

MAR 0 4 2003

Summary of Safety and Effectiveness for CYTO-STAT® tetraCHROME™ CD45-Section 1 D: FITC/CD4-PE/CD8-ECD/CD3-PC5 and CYTO-STAT® tetraCHROME™ CD45-FITC/CD56-PE/CD19-ECD/CD3-PC5 Monoclonal Antibody Reagents

1.0 General Information

Device Generic Name(s):	Lymphocyte Immunophenotyping monoclonal antibodyreagents
Device Trade Name(s):	CYTO-STAT® tetraCHROME™ CD45-FITC/CD4-PE/CD8-ECD/CD3-PC5 and CYTO-STAT® tetraCHROME™ CD45-FITC/CD56-PE/CD19-ECD/CD3-PC5 Monoclonal AntibodyReagents
Device Classification:	CYTO-STAT® tetraCHROME™ CD45-FITC/CD4-PE/CD8-ECD/CD3-PC5 and CYTO-STAT® tetraCHROME™ CD45-FITC/CD56-PE/CD19-ECD/CD3-PC5 Monoclonal AntibodyReagents are Class II medical devices.
Applicant Name and Address:	Beckman Coulter, Inc.Cellular Analysis Division11800 SW 147 AvenueMiami, FL 33196-2500
Date:	February 6, 2003

2.0 Legally Marketed Device(s)

The CYTO-STAT® tetraCHROME™ CD45-FITC/CD4-PE/CD8-ECD/CD3-PC5 and CYTO-STAT® tetraCHROME™ CD45-FITC/CD56-PE/CD19-ECD/CD3-PC5 Monoclonal Antibody Reagents claims substantial equivalence to the previously cleared tetraONE System for EPICS XL Flow Cytometry System with CYTO-STAT® tetraCHROME™ CD45-FITC/CD4-PE/CD8-ECD/CD3-PC5 Monoclonal Antibody Reagent and with CYTO-STAT® tetraCHROME™ CD45-FITC/CD56-PE/CD19-ECD/CD3-PC5 Monoclonal Antibody Reagent

FDA 510(k) Number(s): K990172

3.0 Device Description

The products are:

The CYTO-STAT® tetraCHROME™ CD45-FITC/CD4-PE/CD8-ECD/CD3-PC5 Monoclonal Antibody Reagent and CYTO-STAT® tetraCHROME™ CD45-FITC/CD56-PE/CD19-ECD/CD3-PC5 Monoclonal Antibody Reagent. Each is a combination of four murine monoclonal antibodies, each conjugated to a different fluorochrome and specific for a different cell surface antigen. Specifically.

CYTO-STAT tetraCHROME CD45-FITC/CD4-PE/CD8-ECD/CD3-PC5 . Monoclonal antibody reagent allows the identification and enumeration of Total CD3+ (T cells), Total CD4+, Total CD8+, Dual CD3+/CD4+, Dual CD3+/CD8+ lymphocyte percentages and absolute counts as well as the CD4/CD8 ratio in whole

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blood flow cytometry. When used in conjunction with CD45-FITC/CD56-PE/CD19-ECD/CD3-PC5, the total lymphocyte percentage can be obtained.

CD45-FITC/CD56-PE/CD19-ECD/CD3-PC5 Monoclonal antibody reagent . allows the identification and enumeration of total CD19+ (B cells) and CD3-/CD56+ (NK cells) lymphocyte percentages and absolute counts in whole blood flow cytometry. The total lymphocyte percentage can be obtained as well.

Principle of Method: 4.0

The CYTO-STAT® tetraCHROME™ CD45-FITC/CD4-PE/CD8-ECD/CD3-PC5 and CYTO-STAT® tetraCHROME™ CD45-FITC/CD56-PE/CD19-ECD/CD3-PC5 Monoclonal Antibody Reagents are combinations of four murine monoclonal antibodies, each conjugated to a different fluorochrome and specific for a different cell surface antigen. The test depends on the ability of a monoclonal antibody to bind to the surface of cells expressing discrete antigenic determinants. Red blood cell are lysed and the remaining white blood cells are analyzed on a flow cytometer (COULTER EPICS XL, FC 500 or equivalent flow cytometer). The analysis may be automated, as with XL with System II software which automates standardization of light scatter, fluorescence intensities and adjustment of color compensation settings and tetraONE SYSTEM software which provides automated analysis of lymphocyte subpopulations. Alternatively, the operator may perform the analysis by adjusting and other operational parameters to optimize results when working with non-routine samples.

5.0 Indications for Use:

6.0 Description of the modification:

The currently marketed tetraONE System for EPICS XL Flow Cytometry System with CYTO-STAT® tetraCHROME™ CD45-FITC/CD4-PE/CD8-ECD/CD3-PC5 Monoclonal Antibody Reagent and with CYTO-STAT® tetraCHROME™ CD45-FITC/CD56-PE/CD19-ECD/CD3-PC5 Monoclonal Antibody Reagent is an automated analysis method for simultaneous identification and enumeration of lymphocvte subpopulations (CD3+, CD4+, CD8+, CD19+and CD56+) combining four-color fluorescent monoclonal antibody reagents, quality control reagents, optional absolute count reagent and software. This premarket notification is for the use of the two monoclonal antibody reagent system components as stand alone reagents on any equivalent flow cytometer system, allowing the operator to manually adjust gating and other operational parameters to optimize results at their discretion.

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DEPARTMENT OF HEALTH & HUMAN SERVICES

Image /page/2/Picture/1 description: The image shows the logo for the Department of Health & Human Services USA. The logo is a circular seal with the words "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" arranged around the top half of the circle. Inside the circle is a stylized image of an eagle with its wings spread, facing to the right.

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

Stan Sugrue, Ph.D. Senior Regulatory Affairs Specialist Premarket Product Regulatory Compliance Beckman Coulter, Inc. 11800 SW 147 Avenue MC 31-B06 Miami, Florida 33196-2500

MAR 0 4 2003

K030408 Re:

Trade/Device Name: CYTO-STAT® tetraCHROME™ CD45-FITC/CD4-PE/CD8-ECD/CD3-PC5 and CYTO-STAT® tetraCHROME™ CD45-FITC/CD56-PE/CD19-ECD/CD3-PC5 Monoclonal Antibody Reagents Regulation Number: 21 CFR § 864.5220 Regulation Name: Lymphocyte Immunophenotyping monoclonal antibody reagents Regulatory Class: II Product Code: GKZ Dated: February 6, 2003 Received: February 7, 2003

Dear Dr. Sugrue:

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 either class II (Special Controls) or class III (PMA), 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); 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

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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 information about the application of labeling requirements to your device, or questions on the promotion and advertising of your device, please contact the Office of In Vitro Diagnostic Device Evaluation and Safety at (301) 594-3084. 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 http://www.fda.gov/cdrh/dsma/dsmamain.html.

Sincerely yours,

Steven Putman

Steven I. Gutman, M.D., M.B.A. Director Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health

Enclosure

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INDICATIONS FOR USE Section 1C:

Not assigned 510(k) Number (if known): CYTO-STAT® tetraCHROME™ CD45-FITC/CD4-PE/CD8-Device: ECD/CD3-PC5 and CYTO-STAT® tetraCHROME™ CD45-FITC/CD56-PE/CD19-ECD/CD3-PC5 Monoclonal Antibody Reagents

Indications For Use:

CD45-FITC/CD56-PE/CD19-ECD/CD3-PC5 Monoclonal antibody reagent is intended "For In Vitro Diagnostic Use", allowing the identification and enumeration of total CD19+ (B cells) and CD3-/CD56+ (NK cells) lymphocyte percentages and absolute counts in whole blood flow cytometry. This reagent can also provide the total lymphocyte percentage.

21 CFR 864.5220

Lymphocyte Immunophenotyping monoclonal antibody reagents

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

Concurrence of CDRH, Office of Device Evaluation (ODE)

Prescription Use V (Per 21 CFR 801.109)

Over-The-Counter Use

Churchen Bruton

(Division/Sign/ Division of Clinical Laboratory Devices 510(k) Number 8030408

Beckman Coulter, Inc. Special 510(k): Device Modification TetraCHROME_Rgts_510k.doc

CYTO-STAT® tetraCHROME™ Monoclonal Antibodies

Regulation Number and Section

§ 864.5220 Automated differential cell counter.

(a)
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.(b)
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.”