The FlowCARE PLG CD4 Reagent is for use on the Coulter® EPICS® XL ™/XL-MCL™ or equivalent flow cytometer. The reagent kit combines two fluorescent-labeled monoclonal antibodies in a single reagent formulation. It is intended "For In Vitro Diagnostic Use" for the enumeration of CD4 absolute cell count and CD4 lymphocyte percentage in combination with a White Blood Cell (WBC) Count from a hematology instrument as a dual platform measurement, or independently when used in combination with Flow-Count ™ Fluorospheres as a single platform measurement.

Device Description

The FlowCARE PLG CD4 Reagent consists of a two-color antibody reagent composed of CD45-FITC and CD4-PE. The assay is performed on the EPICS XL, Cytomics FC 500, or equivalent Flow Cytometer using appropriate quality control reagents in combination with an optional absolute count reagent, Flow-Count™ Fluorospheres for determination CD4 absolute counts as a single platform measurement, or in combination with a White Blood Cell Count from a hematology analyzer as a dual platform measurement.

AI/ML Overview

The provided document, K043215, "FlowCARE PLG CD4 Reagent," is a 510(k) summary for a medical device. It does not contain information about acceptance criteria or a study designed to prove the device meets specific acceptance criteria in the typical format of a clinical trial or performance study report.

Instead, this document focuses on demonstrating substantial equivalence to a predicate device. This is a common regulatory pathway for medical devices where the manufacturer shows that their new device is as safe and effective as a legally marketed device (the predicate device) that is already cleared by the FDA.

Therefore, the specific questions outlined in your request related to acceptance criteria, sample size, ground truth, experts, adjudication, MRMC studies, and standalone performance for proving device acceptance are not explicitly addressed or applicable in this type of regulatory submission. The document emphasizes comparison and similarities to an existing cleared device rather than presenting novel performance data against pre-defined acceptance criteria.

Here's why and what information can be extracted or inferred:

Acceptance Criteria and Reported Device Performance: This document does not present a table of acceptance criteria for the FlowCARE PLG CD4 Reagent's performance. Instead, it highlights that the device "claims substantial equivalence" to the predicate device (tetraONE SYSTEM) for the enumeration of CD4 T-Lymphocytes. The "performance" is implicitly deemed acceptable because it is considered equivalent to a device already on the market.
Study Data (Sample Size, Provenance): There is no mention of a specific "test set" sample size or data provenance (country, retrospective/prospective). The document discusses the device's components and intended use, comparing them to the predicate. Any underlying data supporting the "equivalence" would have been part of the manufacturer's internal validation, but it's not detailed in this public summary.
Number of Experts, Qualifications, Adjudication: These details are not relevant for a 510(k) summary of substantial equivalence. No expert review of specific cases or adjudication process is described as the primary mechanism for demonstrating device performance.
MRMC Comparative Effectiveness Study: No MRMC study is mentioned. The focus is on the device's characteristics and its equivalence to a predicate, not on how human readers' performance might improve with or without AI assistance (which is not applicable here as it's a reagent, not an AI system for interpretation).
Standalone Performance: The document describes the reagent's function as an "algorithm only (without human-in-the-loop performance)" is not applicable. The FlowCARE PLG CD4 Reagent is a biological reagent kit used in conjunction with flow cytometers and other laboratory equipment for in vitro diagnostic testing. The performance is the output of the instrument-reagent system.
Type of Ground Truth: The concept of "ground truth" (expert consensus, pathology, outcomes data) is not discussed in the context of validating this device's performance against a standard. The performance is compared to that obtained using a predicate device.
Training Set Sample Size and Ground Truth Establishment: This information is also not included. The device is a diagnostic reagent, not a machine learning algorithm that requires a "training set" in the conventional sense.

In summary, while the request asks for specific details about acceptance criteria and performance studies, the provided document (a 510(k) summary for substantial equivalence) does not contain this information because its purpose is to demonstrate equivalence to an already cleared device, not to present new performance data against pre-defined acceptance criteria in a detailed study report.

Summary

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K043215

Section 1 D: 510(k) Summary of Safety and Effectiveness for FlowCARE PLG CD4 Reagent

1.0 General Information

Applicant Name and Address:	Beckman Coulter, Inc.Cellular Analysis Division11800 SW 147 AvenueMiami, FL 33196-2500
Primary Contact:	Stan Sugrue, Ph.D.Senior Regulatory Affairs SpecialistTelephone: (305) 380-4552FAX: (305) 380-3618E-mail: stan.sugrue@coulter.com
Date:	November 18, 2004
Device Trade Name(s):	FlowCARE™ PLG CD4 Reagent
Device Generic Name(s):	Lymphocyte Immunophenotyping monoclonal antibodyreagents
Device Classification:	The FlowCARE PLG CD4 Reagent is a Class II medicaldevice ((81 GKZ).

2.0 Predicate Device

The FlowCARE PLG CD4 reagent claims substantial equivalence to the tetraONE SYSTEM for EPICS XL Flow Cytometry SYSTEM with CYTO-STAT tetraCHROME CD45-FITC/CD4-RD1/CD8-ECD/CD3-PC5 Monoclonal Antibody Reagent for the enumeration of CD4 T-Lymphocytes,

FDA 510(k) Number(s): K990172

3.0 Device Description

4.0 Principle of Method:

The test depends on 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 the monoclonal antibody reagent. The FlowCARE PLG CD4 Monoclonal Antibody Reagent is a combination of two murine monoclonal antibodies, each conjugated to a specific fluorochrome and specific for different cell surface antigens.

Red blood cells are lysed with the COULTER IMMUNOPREP™ Reagent System and COULTER TQ-PREP™ Workstation or equivalent. The remaining white blood cells are analyzed by flow cytometry using a sequential gating strategy. The total WBC gate is defined in the first histogram (log SS vs CD45-FITC) by the inclusion of all CD45+ events with low, medium and high Side Scatter. A second histogram (log SS vs CD4-PE), gated on the total WBC defined by the first gate, identifies CD4+ lymphocytes by setting a region to include CD40ish'' events with low SS. The CD4% of WBC obtained from this economis used to calculate the CD4 absolute count by multiplication with the WBC count from the hematology analyzer. CD4% of lymphocytes is obtained by defining a lymphocyte in the first histogram identified as the cluster of events exhibiting bright CD45+ fluoresence

Beckman Coulter, Inc. FlowCARE PLG CD4 Reagent

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and low SS. The percentage is obtained by calculation of the CD4+ gated events divided by the CD45+ lymphocyte events.

5.0Comparison	Characteristic	tetraONE System for EPICS XL FlowCytometry System(Predicate)	FlowCARE PLG CD4 Reagent
Similarities	T-Lymphocytesenumeration	Enumerates CD4+T-Lymphocytes	Enumerates CD4+T-Lymphocytes
	Analyticalinstrumentation	Deployed on EPICS® XL-MCL™ flowcytometer	Can be deployed on EPICS®XL-MCL™ flow cytometer
	Analysis Reagents	Uses CYTO-STAT® tetraCHROME™CD45-FITC/CD4-RD1/CD8-ECD/CD3-PC5	CD45-FITC and CD4-PE (RD1)monoclonal dye conjugates areidentical to CD45-FITC/CD4-RD1tetraCHROME™ reagentcomponents
	Analysis Reagents	Uses Flow-Count™ Fluorospheresabsolute count reagent	Can use Flow-Count™Fluorospheres absolute countreagent or equivalent
	Setup Reagents	Flow-Set™ FluorospheresCYTO-COMP™ Cell KitCYTO-COMP™ Reagent Kit	Same or equivalent reagents
	QC Reagents	IMMUNO-TROL™ Control CellsIMMUNO-TROL™ Low ControlCells	Same or equivalent reagents
	Differences	Analysis Reagents	Uses 4-color fluorochrome reagent(CYTO-STAT® tetraCHROME™ CD45-FITC/CD4-RD1/CD8-ECD/CD3-PC5)
Analysis Software		System II™ Automated analysis usingcellSTAT 3D™ algorithm	Manual analysis using customercreated protocols according topackage insert
Flow Cytometer		EPICS® XL-MCL™ flow cytometrysystem only	EPICS XL-MCL, CytomicsFC500, or any equivalent flowcytometry system
Specimen Age		≤ 6 hours (with automatedsoftware)	≤ 120 hours (5 days)*
		≤ 72 hours (without automatedsoftware, tetraCHROME CD45-FITC/CD4-RD1/CD8-ECD/CD3-PC5)	* The specimen age limit for dualplatform measurement isdependent upon the claims forthe hematology analyzer but notto exceed five days.
Intended Use		Enumeration of total T, B, andNK lymphocytesEnumeration of three major T-lymphocyte subset populations	Enumeration of CD4+T-Lymphocytes only

Comparison to Predicate 5.0

Indications for Use: (Intended Use Statement from Package insert) 6.0

The FlowCARE PLG CD4 Reagent is for use on the COULTER® EPICS® XL™/XL-MCL™ or equivalent flow cytometer. The reagent kit combines two fluorescent-labeled monoclonal antibodies in a sincle reacent formulation. It is intended "For In Vitro Diagnostic Use" for the enumeration of CD4 absolute cell count and CD4 lymphocyte percentage in combination with a White Blood Cell (WBC) Count from a hematology instrument as a dual platform measurement, or independently when used in combination with Flow-Count™ Fluorospheres as a single platform measurement.

7.0 Conclusion:

The FlowCARE™ PLG Reagent is substantially equivalent 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 for the enumeration of the CD4 T-Lymphocyte subpopulation.

Beckman Coulter, Inc. FlowCARE PLG CD4 Reagent

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DEPARTMENT OF HEALTH & HUMAN SERVICES

Image /page/2/Picture/1 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" around the perimeter. Inside the circle is a stylized symbol that resembles a caduceus, a traditional symbol of medicine, but with three wavy lines instead of snakes.

JAN 1 9 2005

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 S.W. 147th Avenue P.O. Box 169015 Miami, FL 33116-9015

Re: K043215

Trade/Device Name: FlowCARE™ PLG CD4 Reagent Regulation Number: 21 CFR 864.5220 Regulation Name: Automated differential cell counter Regulatory Class: Class II Product Code: GKZ Dated: November 22, 2004 Received: November 23, 2004

Dear Dr. Sugrue:

We have reviewed your Section 510(k) premarket notification of intent to market the device we nave reviewed your we determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate for ase stared in the energently 76, 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 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.

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Page 2 -

If you desire specific information about the application of labeling requirements to your device, or guestions on the promotion and advertising of your device, please contact the Office of In Vitro Diagnostic Device Evaluation and Safety at (240) 276-0484. 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/industry/support/index.html

Sincerely yours,

Robert Beckerh

Robert L. Becker, Jr., MD, Pa Director Division of Immunology and Hematology Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health

Enclosure

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Section 1C:

INDICATIONS FOR USE

510(k) Number (if known):

Not assigned K043215

Device:

FlowCARE™ PLG CD4 Reagent

Intended Use

The FlowCARE PLG CD4 Reagent provides the ability to measure CD4+ cells by utilizing a panleukocyte gating (PLG) approach where CD4+ T-cell enumeration is based on the use of all leukocytes, instead of on lymphocytes only, as the matching common denominator between the hematology generated WBC and the flow cytometric enumeration. A sequential gating strategy is used to include all CD45+ leukocytes and to measure the CD4+% of total leukocyte values generated from this gate.

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 Use (Per 21 CFR 801.109)

Over-The-Counter

Juxhine Kiu lahte

Division/Sign-Off

Office of In Vitro Diagnostic Device
Evaluation and Safety

K043215
510(k)

Beckman Coulter, Inc. FlowCARE PLG CD4 Reagent

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.”