The Sysmex® XT-4000i is a quantitative multi-parameter automated hematology analyzer intended for in vitro diagnostic use in screening patient populations found in clinical laboratories. The XT-4000i classifies and enumerates the following parameters for whole blood: WBC, RBC, HGB, HCT, MCV, MCH, MCHC, PLT, NEUT%/#, LYMPH%/#, MONO%/#, EO%/#, BASO%/#, IG%/#, RDW-CV, RDW-SD, MPV, RET%/#, IRF, RET-He and has a Body Fluid mode for body fluids. The Body Fluid mode enumerates the WBC-BF, RBC-BF, MN%/#, PMN%/# and TC-BF# parameters in cerebrospinal fluids (CSF), serous fluids (peritoneal, pleural) and synovial fluids. Serous and Synovial fluids should be collected in K2EDTA to prevent clotting of fluid. The use of anticoagulants with CSF specimens is not required or recommended.

Device Description

The XT-4000 i is the same as the XT-2000 i which is part of the XT- Series and has a Body Fluid mode the same as the XE-5000. It is an automated hematology analyzer which consists of four principle units: (1) Main Unit which aspirates, dilutes, mixes, and analyzes whole blood and body fluid samples; (2) Sampler Unit which supplies samples to the Main Unit automatically; (3) IPU (Information Processing Unit) which processes data from the Main Unit and provides the operator interface with the system; (4) Pneumatic Unit which supplies pressure and vacuum from the Main Unit.

The Body Fluid analysis mode of the XT-4000 i uses the 4DIFF scattergram & the RBC distribution obtained from a specialized analysis sequence to calculate & display the WBC (WBC-BF) counts, mononuclear cell (MN) / polymorphonuclear cell (PMN) counts & percentages, TC-BF (Total Count) & RBC (RBC-BF) counts found in the body fluid.

AI/ML Overview

Acceptance Criteria and Device Performance Study for Sysmex® XT-4000i Automated Hematology Analyzer

This response summarizes the acceptance criteria and the study conducted to demonstrate the Sysmex® XT-4000i Automated Hematology Analyzer meets these criteria, based on the provided 510(k) submission information.

1. Table of Acceptance Criteria and Reported Device Performance

The acceptance criteria for the Sysmex® XT-4000i are implicitly established by demonstrating substantial equivalence to its predicate device, the XE-5000 Body Fluid Mode, across various performance metrics. The submission focuses on proving that the XT-4000i's Body Fluid mode performs equivalently to the XE-5000's Body Fluid mode for the enumerated parameters.

Acceptance Criteria (Measured Performance Aspect)	Reported Device Performance (Sysmex® XT-4000i vs. XE-5000 Body Fluid Mode)
Accuracy (for Body Fluid mode parameters: WBC-BF, RBC-BF, MN%/#, PMN%/#, TC-BF#)	Data collected indicated equivalent performance between the XT-4000i and XE-5000 Body Fluid Mode.
Precision (for Body Fluid mode parameters: WBC-BF, RBC-BF, MN%/#, PMN%/#, TC-BF#)	Data collected indicated equivalent performance between the XT-4000i and XE-5000 Body Fluid Mode.
Linearity (for Body Fluid mode parameters: WBC-BF, RBC-BF, MN%/#, PMN%/#, TC-BF#)	Data collected indicated equivalent performance between the XT-4000i and XE-5000 Body Fluid Mode.
Carryover (for Body Fluid mode parameters: WBC-BF, RBC-BF, MN%/#, PMN%/#, TC-BF#)	Data collected indicated equivalent performance between the XT-4000i and XE-5000 Body Fluid Mode.
Overall Performance	Results indicated equivalent performance to the XE-5000 Body Fluid Mode, supporting substantial equivalence.

Note: The submission implies that the acceptance criteria for these parameters are the manufacturer's specifications, which the XT-4000i's Body Fluid mode met, thereby demonstrating equivalency to the predicate device.

2. Sample Size Used for the Test Set and Data Provenance

The provided summary does not explicitly state the specific numerical sample size used for the test set or the data provenance (e.g., country of origin of the data, retrospective or prospective). It only states that "Studies were performed to evaluate the equivalency of the XT-4000i to the XE-5000 Body Fluid Mode." and "Data consisting of Accuracy, Precision, Linearity and Carryover was collected to show performance to the manufacturer's specification for the Body Fluid mode."

Without more detailed study reports, these specifics cannot be determined from the available text.

3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts

This information is not provided in the submitted summary. Hematology analyzer performance studies typically involve comparison to reference methods or manual counts, but the involvement and qualifications of specific "experts" for ground truth establishment are not detailed here.

4. Adjudication Method for the Test Set

This information is not provided in the submitted summary. Given the nature of a hematology analyzer, ground truth is usually established through comparative testing with established reference methods rather than through expert adjudication in the same way an imaging or diagnostic AI might require.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was done, and the effect size of how much human readers improve with AI vs without AI assistance

A Multi-Reader Multi-Case (MRMC) comparative effectiveness study was not performed. This type of study is typically relevant for interpretative devices where human readers' performance is augmented by an AI. The Sysmex® XT-4000i is an automated hematology analyzer, which performs direct measurement and enumeration, not an interpretative AI requiring human readers.

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

Yes, the study demonstrating the performance of the Sysmex® XT-4000i was a standalone performance study. The device is an automated analyzer, meaning it operates without human intervention in the analysis process once the sample is loaded. The performance data for accuracy, precision, linearity, and carryover directly reflect the algorithm's and hardware's capabilities in analyzing the body fluid parameters.

7. The Type of Ground Truth Used

The ground truth used for evaluating the Sysmex® XT-4000i's Body Fluid mode performance would have been established by comparison to established reference methods (e.g., manual cell counts, other validated automated analyzers, or calibrated standards) for the relevant parameters (WBC-BF, RBC-BF, MN%/#, PMN%/#, TC-BF#). The submission states that the performance was shown "to the manufacturer's specification," which implies these specifications are validated against recognized reference standards.

8. The Sample Size for the Training Set

The concept of a "training set" is not applicable in the context of this device's submission. The Sysmex® XT-4000i is an automated hematology analyzer based on established measurement principles (Hydro Dynamic Focusing, flow cytometry, SLS-hemoglobin method), not a machine learning or AI-driven diagnostic device that requires explicit training data in the same way. Its development would involve calibration and validation, but not a "training set" as understood in AI/ML.

9. How the Ground Truth for the Training Set was Established

As stated above, the device does not utilize a "training set" in the context of AI/ML. Its operational parameters and algorithms are designed based on physical and chemical principles of cell analysis, and its accuracy is validated against known standards and reference methods during its development and testing.

Summary

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5. 510(k) SUMMARY OF SAFETY AND EFFECTIVENESS

This summary of 510(k) safety and effectiveness information is being submitted in accordance with the requirements of SMDA 1990 and 21 CFR 807.92. The assigned 510(k) number is: K091313_______________________________________________________________________________________________________________________________________

1. Submitted by:	Sysmex America, Inc.One Nelson C. White ParkwayMundelein, IL. 60060Phone: (847) 996-4618; FAX: (847) 996-4655Contact person: Sharita BrooksDate prepared: April 30, 2009
2. Name of Device:	Trade or proprietary name: Sysmex® XT-4000 Common name: Automated Hematology AnalyzerClassification name: Automated Differential Cell Counter21 CFR 864.5220
3. Predicate Device:	Sysmex® XT-SeriesSysmex® XE-5000, Body Fluid Mode
4. Device Description:	The XT-4000 is the same as the XT-2000 which is part of the XT-Series and has a Body Fluid mode the same as the XE-5000. It is anautomated hematology analyzer which consists of four principle units:(1) Main Unit which aspirates, dilutes, mixes, and analyzes whole bloodand body fluid samples; (2) Sampler Unit which supplies samples to theMain Unit automatically; (3) IPU (Information Processing Unit) whichprocesses data from the Main Unit and provides the operator interfacewith the system; (4) Pneumatic Unit which supplies pressure andvacuum from the Main Unit.The Body Fluid analysis mode of the XT-4000 uses the 4DIFFscattergram & the RBC distribution obtained from a specialized analysissequence to calculate & display the WBC (WBC-BF) counts,mononuclear cell (MN) / polymorphonuclear cell (PMN) counts &percentages, TC-BF (Total Count) & RBC (RBC-BF) counts found inthe body fluid.
5. Intended Use:	The Sysmex® XT-4000 is a quantitative multi-parameter automatedhematology analyzer intended for in vitro diagnostic use in screeningpatient populations found in clinical laboratories. The XT-4000 classifies and enumerates the following parameters for whole blood:WBC, RBC, HGB, HCT, MCV, MCH, MCHC, PLT, NEUT%/#,LYMPH%/#, MONO%/#, EO%/#, BASO%/#, IG%/#, RDW-CV,RDW-SD, MPV, RET%/#, IRF, RET-He and has a Body Fluid modefor body fluids. The Body Fluid mode enumerates the WBC-BF, RBC-BF, MN%/#, PMN%/# and TC-BF# parameters in cerebrospinal fluids(CSF), serous fluids (peritoneal, pleural) and synovial fluids. Serousand Synovial fluids should be collected in K2EDTA to prevent clottingof fluid. The use of anticoagulants with CSF specimens is not requiredor recommended.
6. Substantial equivalence-similarities and differences	The following table compares the XT-4000 with the XT-Series and theXE-5000 Body Fluid Mode.
7. Clinical PerformanceData:	Studies were performed to evaluate the equivalency of the XT-4000 tothe XE-5000 Body Fluid Mode. Results indicated equivalentperformance.
8. Conclusions:	The performance data demonstrated substantial equivalence.

Sysmex XT-4000i Automated Hematology Analyzer

510(k) FDA Submission

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Features(Submission #)	XT-4000 i	XT-Series(K021241)25-June-02	XE-5000(K071967)20-Nov-07
FDA Clearance
Intended Use	The Sysmex® XT-4000 i isa quantitative multi-parameter automatedhematology analyzerintended for in vitrodiagnostic use in screeningpatient populations foundin clinical laboratories.The XT-4000 i classifiesand enumerates thefollowing parameters forwhole blood: WBC, RBC,HGB, HCT, MCV, MCH,MCHC, PLT, NEUT%/#,LYMPH%/#, MONO%/#,EO%/#, BASO%/#,IG%/#, RDW-CV, RDW-SD, MPV, RET%/#, IRF,RET-He and has a BodyFluid mode for bodyfluids. The Body Fluidmode enumerates theWBC-BF, RBC-BF,MN%/#, PMN%/# andTC-BF# parameters incerebrospinal fluids (CSF),serous fluids (peritoneal,pleural) and synovialfluids. Serous andSynovial fluids should becollected in K₂EDTA toprevent clotting of fluid.The use of anticoagulantswith CSF specimens is notrequired or recommended.	The Sysmex® XT-2000 i isintended for in vitrodiagnostic use in theclinical laboratory as amulti-parameterhematology analyzer.The XT-2000 i has a BodyFluid Application whichadds a quantitative,automated procedure foranalyzing body fluids(cerebrospinal fluids(CSF), serous fluids, andsynovial fluids withEDTA, as needed) to theXT-2000 i , providingenumeration of the WBCsand the RBCs.	The Sysmex® XE-5000 isan automated hematologyanalyzer for in vitrodiagnostic use in screeningpatient populations foundin clinical laboratories.The XE-5000 has a BodyFluid mode for bodyfluids. The Body Fluidmode analyzes WBC-BF,RBC-BF, MN%/#,PMN%/# and TC-BF# inbody fluids (cerebrospinalfluids (CSF), serous fluids,and synovial fluids withEDTA, as needed).
Sample Type	Whole blood/Body Fluids	Whole blood/Body Fluids	Whole blood/Body Fluids
Parameters	WBC, RBC, HGB, HCT,MCV, MCH, MCHC,PLT, NEUT%/#,LYMPH%/#, MONO%/#,EO%/#, BASO%/#,RDW-CV, RDW-SD,MPV, RET%/#, IRF,IG%/#, RET-He#	WBC, RBC, HGB, HCT,MCV, MCH, MCHC,PLT, NEUT%/#,LYMPH%/#, MONO%/#,EO%/#, BASO%/#,RDW-CV, RDW-SD,MPV, RET%/#, IRF,IG%/#, RET-He#	WBC, RBC, HGB, HCT,MCV, MCH, MCHC,PLT, NEUT%/#,LYMPH%/#, MONO%/#,EO%/#, BASO%/#,NRBC%/#,RDW-CV,RDW-SD, MPV, RET%/#,IRF, IG%/#, HPC#, RET-He#, IPF.
	Body Fluid Mode:WBC-BF, RBC-BF,MN%/#, PMN%/#, TC-	Body Fluid Application:WBC-BF, RBC-BF	Body Fluid Mode:WBC-BF, RBC-BF,MN%/#, PMN%/#, TC-
	BF#		BF#
Reagents	CELLPACKTM (Diluent)STROMATOLYSER-FBTM (Lyse)STROMATOLYSER-4DLTM (Lyse)STROMATOLYSER-4DSTM (Stain)SULFOLYSER (Lyse)RET-SEARCH II(Diluent)RET-SEARCH II (Stain)	CELLPACKTM (Diluent)STROMATOLYSER-FBTM (Lyse)STROMATOLYSER-4DLTM (Lyse)STROMATOLYSER-4DSTM (Stain)SULFOLYSER (Lyse)RET-SEARCH II(Diluent)RET-SEARCH II (Stain)	CELLPACKTM (Diluent)CELLSHEATHTM(Diluent)STROMATOLYSER-FBTM (Lyse)STROMATOLYSER-4DLTM (Lyse)STROMATOLYSER-4DSTM (Stain)STROMATOLYSER-NRTM (Diluent)STROMATOLYSER-NRTM (Stain)STROMATOLYSER-IMTM (Lyse)SULFOLYSER (Lyse)RET-SEARCH II(Diluent)RET-SEARCH II (Stain)
Principles	Performs hematologyanalyses according tothe Hydro DynamicFocusing (DC Detection),flow cytometrymethod (using asemiconductor laser), andSLS-hemoglobinmethod.	Performs hematologyanalyses according tothe Hydro DynamicFocusing (DC Detection),flow cytometrymethod (using asemiconductor laser), andSLS-hemoglobinmethod.	Performs hematologyanalysis according tothe RF/DC detectionmethod, Hydro DynamicFocusing (DC Detection),flow cytometry method(using a semiconductorlaser), and SLS-hemoglobin method.
Dimensions(HxWxD) (mm)	630x520x720	630x520x720	711x706x535
Weight (kg)	59	59	81
Quality Control/Calibrator	e-Check (XE) – 3 LevelsCalibrator (X Cal)	e-Check - 3 LevelsCalibrator (X Cal)	e-Check (XE) - 3 LevelsXE Calibrator (X Cal)
Software/HardwareDifferences	The XT-4000i performsthe same as the XT-2000iand has a Body Fluidmode the same as the XE-5000.	The XT-2000i does nothave a Body Fluid mode .The XT-2000i has a BodyFluid Application.	The XE-5000 has a BodyFluid mode .
Throughput	Approx 80-100/hrDepending on mode used.	Approx 80Depending on mode used.	Approximately 113-150depending on mode used.
Equivalency Data	Data consisting of Accuracy,Precision, Linearity andCarryover was collected toshow performance to themanufacturer's specificationfor the Body Fluid mode.This analysis supports theclaim that the XT-4000i BodyFluid mode is substantiallyequivalent to the XE-5000Body Fluid mode.	Proven performance in FDAsubmission	Proven performance in FDAsubmission

Table 1: Substantial Equivalence – Similarities and Differences to the XT-Series and I

Sysmex XT-4000i Automated Hematology Analyzer
510(k) FDA Submission

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ﺮ

Sysmex XT-4000i Automated Hematology Analyzer
510(k) FDA Submission

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Image /page/3/Picture/0 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a stylized depiction of an eagle or bird-like figure with three curved lines representing its wings or body. The bird is positioned within a circular border. The text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" is arranged around the upper portion of the circle.

DEPARTMENT OF HEALTH & HUMAN SERVICES

Public Health Service

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

Sysmex America, Inc. c/o Ms. Sharita Brooks, BBA, MT Clinical Affairs Specialist One Nelson C. White Parkway Mundelein, IL 60060

MAR 3 0 2010

Re: K091313

Trade/Device Name: Sysmex XT-4000i Regulation Number: 21 CFR 864.5220 Regulation Name: Automated differential cell counter Regulatory Class: Class II Product Code: GKZ Dated: March 18, 2010 Received: March 19, 2010

Dear Ms. Brooks:

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 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

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Page 2 - Ms. Sharita Brooks

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 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 (301) 796-5450. 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 (800) 638-2041 or (301) 796-7100 or at its Internet address http://www.fda.gov/cdrh/industry/support/index.html.

Sincerely vours.

Mana M Chan

Maria M. Chan. Ph.D. Director Division of Immunology and Hematology Devices Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health

Enclosure

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Indications for Use Form

510(k) Number (if known) K091313

Device Name: XT-4000i, Automated Hematology Analyzer

Indications for Use:

The Sysmex® XT-4000i is a quantitative multi-parameter automated hematology analyzer intended for in vitro diagnostic use in screening patient populations found in clinical laboratories. The XT-4000i classifies and enumerates the following parameters for whole blood: WBC, RBC, HCT, MCV, MCH, MCHC, PLT, NEUT%/#, LYMPH%/#, MONO%/#, EO%/#, BASO%/#, IG%/#, RDW-CV, RDW-SD, MPV, RET%/#, IRF, RET-He and has a Body Fluid mode for body fluids. The Body Fluid mode enumerates the WBC-BF, RBC-BF, MN%/#, PMN%/# and TC-BF# parameters in cerebrospinal fluids (CSF), serous fluids (peritoneal, pleural) and synovial fluids. Serous and Synovial fluids should be collected in K2EDTA to prevent clotting of fluid. The use of anticoagulants with CSF specimens is not required or recommended.

Prescription Use (Part 21 CFR 801 Subpart D) AND/OR

Over-The-Counter Use (21 CFR 801 Subpart C)

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

Concurrence of CDRH, Office of In Vitro Diagnostic Devices (OIVD)

Seuk R.K.

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

510(k)	K091313
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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.”