The XN-Series modules (XN-11, XN-21) are quantitative multi-parameter automated hematology analyzers intended for in vitro diagnostic use in screening patient populations found in clinical and reference laboratories.

The XN-Series modules classify and enumerate the following parameters in whole blood: WBC, RBC, HCT, MCV, MCH, MCHC, PLT, NEUT%H, LYMPH%#, MONO%#, E0%#, BASO%#, IG%#, RDW-SD, MPV, NRBC#/%, RET%/#, IPF, IRF, RET-He and has a Body Fluid mode for body fluids. The Body Fluid mode enumerates the WBC-BF, RBC-BF, MN%#, and TC-BF parameters in body fluids (peritoneal, pleural and synovial). Whole blood should be collected in K2 or K3EDTA anticoagulant and peritoneal, pleural and synovial fluids in K2EDTA anticoagulant to prevent clotting of fluid.

Device Description

The Sysmex® XN-Series modules (XN-11, XN-21) are multi-parameter hematology analyzers intended to perform tests on whole blood samples collected in K2 or K3EDTA anticoagulant and body fluids (pleural, peritoneal and synovial) collected in K2 anticoagulant. The XN-Series modules (XN-11, XN-21) are part of the family of XN-Series devices (K112605) cleared Oct 19, 2012 with modifications to stabilize the HCT/MCV parameters to within +8% at room temperature (18-26°C) for 24 hours and refrigerated temperature (2-8°C) for 48 hours for commercial and reference laboratories. The difference between the XN-11 and XN-21 is the presence of the WPC Channel in the XN-21.

The instrument consists of four principal units: (1) Two Main Units (XN-11, XN-21) which aspirate, dilute, mix, and analyze blood and body fluid samples; (2) Two Auto Sampler Units (SA-10 for a single module, or SA-20 for two modules) which supply 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 XN-Series analyzers perform analysis using the following methods: Sheath Flow DC Detection Method, and Flow Cytometry Methods using a Semiconductor Laser. Particle characterization and identification is based on detection of forward scatter, fluorescence and adaptive cluster analysis. The XN-Series analyzers automatically classify cells from whole blood and body fluids and carry out all processes automatically from aspiration of the sample to outputting the results.

The body fluid analysis mode of the XN-Series analyzers 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, Total Count (TC-BF) & RBC (RBC-BF) counts found in the body fluid.

Analysis results and graphics are displayed on the IPU screen. They can be printed on any of the available printers or transmitted to a Host computer.

AI/ML Overview

The provided text describes the Sysmex® XN-Series (XN-11, XN-21) Automated Hematology Analyzers and their substantial equivalence to the Sysmex® XE-5000 Automated Hematology Analyzer.

Here's an analysis of the acceptance criteria and the study proving the device meets them, based on the provided document:

1. Table of Acceptance Criteria and Reported Device Performance:

The document doesn't explicitly state "acceptance criteria" in a neat table format for all parameters. Instead, it states that "Data consisting of Accuracy, Precision, Linearity and Carryover were collected to show performance to the manufacturer's specification for the Whole Blood and Body Fluid mode." It then broadly concludes that "This analysis supports the claim that the XN-Series analyzers are substantially equivalent to the XE-5000."

To infer the acceptance criteria and a "reported device performance," we would need the actual study reports for Accuracy, Precision, Linearity, and Carryover, which are not detailed in this summary. The summary only broadly states that the studies were performed and indicated equivalent performance.

Therefore, a table of explicit acceptance criteria and corresponding reported device performance values cannot be fully constructed from the given text. The document states that the performance met the manufacturer's specifications and showed equivalence to the predicate device.

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

The document mentions that "Studies were performed to evaluate the equivalency of the XN-Series Automated Hematology analyzers (Modules XN-11, XN-21) to the XE-5000 Automated Hematology analyzer." However, it does not specify the sample size used for these equivalency studies.

Regarding data provenance, the document does not explicitly state the country of origin of the data or whether the studies were retrospective or prospective.

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

The document does not provide any information about experts used to establish ground truth or their qualifications. Given that this is an automated hematology analyzer, the ground truth is typically established by reference methods or comparison to a predicate device, rather than expert interpretation of images or clinical assessments.

4. Adjudication Method for the Test Set:

The document does not describe any adjudication method. This is expected as the device is an automated analyzer, and adjudication (e.g., 2+1, 3+1) is typically relevant for human interpretation of data, where discrepancies between readers need a defined resolution process.

5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study:

A Multi-Reader Multi-Case (MRMC) comparative effectiveness study was not explicitly mentioned or described. This type of study is more common for diagnostic imaging devices where human readers interpret medical images with and without AI assistance. The Sysmex XN-Series is an automated hematology analyzer, so its primary function is direct measurement and classification, not as an AI assistance tool for human interpretation in the context of MRMC studies.

6. Standalone (Algorithm Only Without Human-in-the-Loop Performance) Study:

Yes, the studies described are inherently standalone performance evaluations of the automated hematology analyzer. The device itself is designed for automated classification and enumeration of blood and body fluid parameters without human intervention in the primary measurement process. The "Accuracy, Precision, Linearity and Carryover" studies evaluate the device's technical performance independently.

7. Type of Ground Truth Used:

The ground truth for the performance studies (Accuracy, Precision, Linearity, and Carryover) would have been established by:

Comparison to a predicate device (Sysmex® XE-5000 Automated Hematology Analyzer): The core of the 510(k) submission is to demonstrate substantial equivalence to this predicate. This means results from the XN-Series would be compared against results from the XE-5000.
Reference Methods: For parameters like cell counts, hemoglobin, etc., ground truth often involves established reference methods, although these are not explicitly detailed in the summary.
Manufacturer's Specifications: The document states performance was shown "to the manufacturer's specification," implying these specifications serve as an internal ground truth or target for performance.

8. Sample Size for the Training Set:

The document does not provide any information about a training set or its sample size. Automated hematology analyzers typically use algorithms developed through extensive R&D, and while there's an internal "training" process for the algorithms, it's not usually presented as a distinct "training set" in the same way machine learning models are for regulatory submissions in other domains. The performance studies described are validation or test sets.

9. How the Ground Truth for the Training Set Was Established:

Since no training set information is provided, how its ground truth was established is not stated in the document.

Summary

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Image /page/0/Picture/1 description: The image is a black and white logo for the U.S. Department of Health & Human Services. The logo features the department's name in a circular arrangement around an emblem. The emblem is a stylized design of three human profiles facing right, with a wing-like shape above them, symbolizing health and human services.

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

December 5, 2014

Sysmex America, Inc. c/o Ms. Sharita Brooks Manager Clinical Affairs 577 Aptakisic Road Lincolnshire, IL. 60069

Re: K141681

Trade/Device Name: Sysmex® XN-Series (XN-11, XN-21) Automated Hematology Analyzers Regulation Number: 21 CFR 864.5220 Regulation Name: Automated differential cell counter Regulatory Class: Class II Product Code: GKZ Dated: October 30, 2014 Received: October 31, 2014

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. 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 CFR Part 807); labeling (21 CFR Part 801); medical device reporting (reporting of medical

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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 Part 801), please contact the Division of Industry and Consumer Education at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address

http://www.fda.gov/MedicalDevices/Resourcesfor You/Industry/default.htm. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR 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 Industry and Consumer Education at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address

http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm.

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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Indications for Use

510(k) Number (if known) K141681

Device Name

XN-Series (XN-11, XN-21) Automated Hematology Analyzers

Indications for Use (Describe)

Type of Use (Select one or both, as applicable)

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

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005 510(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: _______________________________________________________________________________________________________________________________________________

1. Submitted by:	Sysmex America, Inc.577 Aptakisic RoadLincolnshire, IL. 60069Phone: (224) 543-9618; FAX: (224) 543-4699Contact person: Sharita BrooksDate prepared: June 19, 2014
2. Name of Device:	Trade or proprietary name: Sysmex® XN-Series (XN-11, XN-21)Common name: Automated Hematology AnalyzerClassification name: Automated Differential Cell Counter 21 CFR 864.5220 is aClass II device. Product Code: GKZRelated Items:
	Product Code: 81 GIFCELLPACK® DCL (Diluent) – K112605CELLPACKTM DFL (Diluent) – K112065CELLSHEATH(C)TM (Diluent) – K051459
	Product Code: 81 GGKLysercellTM WNR (Lyse) – K112605LysercellTM WDF (Lyse) – K112605LysercellTM WPC (Lyse) – K112605
	Product Code: 81 KJKFluorocellTM WNR (Stain) – K112605FluorocellTM WDF (Stain) – K112605FluorocellTM RET (Stain) – K112065FluorocellTM PLT (Stain) – K112605FluorocellTM WPC (Stain) – K112605
	Product Code: 81 KSAXN CAL (Calibrator) - K120745XN CAL PF (Calibrator) - K120747
	Product Code: 81 JPKXN CHECK (Control) – K120742XN CHECK BF (Control) – K120744
	Analyzer ComponentsSA-10 (Auto Sampler for single module)SA-20 (Auto Sampler for two modules)IPU (Information Processing Unit)
3. Predicate Device:	Sysmex® XE-5000Automated Hematology Analyzer
4. Device Description:	The Sysmex® XN-Series modules (XN-11, XN-21) are multi-parameter hematology analyzers intended to perform tests on whole blood samples collected in K2 or K3EDTA anticoagulant and body fluids (pleural, peritoneal and synovial) collected in K2 anticoagulant. The XN-Series modules (XN-11, XN-21) are part of the family of XN-Series devices (K112605) cleared Oct 19, 2012 with modifications to stabilize the HCT/MCV parameters to within +8% at room temperature (18-26°C) for 24 hours and refrigerated temperature (2-8°C) for 48 hours for commercial and reference laboratories. The difference between the XN-11 and XN-21 is the presence of the WPC Channel in the XN-21.The instrument consists of four principal units: (1) Two Main Units (XN-11, XN-21) which aspirate, dilute, mix, and analyze blood and body fluid samples; (2) Two Auto Sampler Units (SA-10 for a single module, or SA-20 for two modules) which supply 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 XN-Series analyzers perform analysis using the following methods: Sheath Flow DC Detection Method, and Flow Cytometry Methods using a Semiconductor Laser. Particle characterization and identification is based on detection of forward scatter, fluorescence and adaptive cluster analysis. The XN-Series analyzers automatically classify cells from whole blood and body fluids and carry out all processes automatically from aspiration of the sample to outputting the results.The body fluid analysis mode of the XN-Series analyzers 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, Total Count (TC-BF) & RBC (RBC-BF) counts found in the body fluid.Analysis results and graphics are displayed on the IPU screen. They can be printed on any of the available printers or transmitted to a Host computer.
5. Intended Use:	The XN-Series modules (XN-11, XN-21) are quantitative multi-parameter automated hematology analyzers intended for in vitro diagnostic use in screening patient populations found in clinical and reference laboratories.The XN-Series modules classify and enumerate the following parameters in whole blood: WBC, RBC, HGB, HCT, MCV, MCH, MCHC, PLT, NEUT%/#, LYMPH%/#, MONO%/#, EO%/#, BASO%/#, IG%/#, RDW-CV, RDW-SD, MPV, NRBC#/%, RET%/#, IPF, 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 body fluids (peritoneal, pleural and synovial). Whole blood should be collected in K2 or K3EDTA anticoagulant and peritoneal, pleural and synovial fluids in K2EDTA anticoagulant to prevent clotting of fluid.
6. Substantial equivalence-similarities and differences	The following table compares the XN-Series modules (XN-11, XN-21) Automated Hematology analyzers with the XE-5000 Automated Hematology analyzer.
7. Clinical Performance Data:	Studies were performed to evaluate the equivalency of the XN-Series Automated Hematology analyzers (Modules XN-11, XN-21) to the XE-5000 Automated Hematology analyzer. Results indicated equivalent performance.
Item	Predicate XE-5000(K071967)20-Nov-07	Device XN-Series(XN-11, XN-21)
Intended Use	Sysmex® XE-5000 is an automatedhematology analyzer for in vitrodiagnostic use in screening patientpopulations found in clinicallaboratories. The XE-5000 classifiesand enumerates the same parameters asthe XE-2100 using whole blood asdescribed below, cord blood for HPCand has a body fluid mode for bodyfluids. The Body Fluid mode analyzesWBC-BF, RBC-BF, MN%/#, PMN%/#and TC-BF in body fluids(cerebrospinal fluids (CSF), serousfluids, and synovial fluids with EDTA,as needed).WBC, RBC, HGB, HCT, MCV, MCH,MCHC, PLT, NEUT% / #, LYMPH% /#, ΜΟΝΟ% / #, EO% / #, BASO% / #,NRBC% / #, RDW-SD, RDW-CV,MPV, RET% / #, IRF, IG% / #,RET-He, IPF, HPC WBC-BF,RBC-BF, MN% / #, PMN%/ #,TC-BF#.	The XN-Series modules (XN-11, XN-21)are quantitative multi-parameter automatedhematology analyzers intended for in vitrodiagnostic use in screening patientpopulations found in clinical and referencelaboratories.The XN-Series modules classify andenumerate the following parameters inwhole blood: WBC, RBC, HGB, HCT,MCV, MCH, MCHC, PLT, NEUT%/#,LYMPH%/#, MONO%/#, EO%/#,BASO%/#, IG%/#, RDW-CV, RDW-SD,MPV, NRBC#/%, RET%/#, IPF, IRF,RET-He and has a Body Fluid mode forbody fluids. The Body Fluid modeenumerates the WBC-BF, RBC-BF,MN%/#, PMN%/#, and TC-BF parametersin body fluids (peritoneal, pleural andsynovial). Whole blood should becollected in K2 or K3EDTA anticoagulantand peritoneal, pleural and synovial fluidsin K₂EDTA anticoagulant to preventclotting of fluid.
Equivalency Data	Proven performance in FDAsubmission	Data consisting of Accuracy, Precision,Linearity and Carryover were collected toshow performance to the manufacturer'sspecification for the Whole Blood andBody Fluid mode. This analysis supportsthe claim that the XN-Series analyzers aresubstantially equivalent to the XE-5000.
Similarities
Specimen Type	Whole Blood and Body Fluids (Serous,Synovial)	SAME
Test Principle	Performs hematology analysesaccording to the Hydro DynamicFocusing (DC Detection), flowcytometry method (using asemiconductor laser), and SLS-hemoglobin method.	SAME
Parameters	Whole Blood Mode:WBC, RBC, HGB, HCT, MCV, MCH,MCHC, PLT, NEUT%/#, LYMPH%/#,ΜΟΝΟ%/#, ΕO%/#, BASO%/#,NRBC%/#, RDW-CV, RDW-SD,MPV, RET%/#, IRF, IG%/#, RET-He,IPF.Body Fluid Mode:WBC-BF, RBC-BF, MN%/#,PMN%/#, TC-BF#	SAME

Reagents	SULFOLYSER (Lyse)	SAME
	Sampler Analysis Mode
Modes of Operation	Manual Closed Analysis Mode	SAME
	Body Fluid Analysis Mode
Measuring Channels	RBC/PLTRET	SAME
	Differences
Item	Predicate XE-5000(K071967)20-Nov-07	Device XN-Series(XN-11, XN-21)
Specimen type	Body Fluid - CSFUmbilical Cord Blood	Not Available
Test Principal	RF/DC detection method	Not Available
Controls & Calibrators	Whole Bloode-Check (XE) – 3 LevelsX CAL (XE Calibrator)Not Available	Whole BloodXN CHECK - 3 LevelsXN CAL (XN-Series Calibrator)XN CAL PF (Platelet F Calibrator)

	Body FluidNot Available	Body FluidXN CHECK BF - 2 Levels
IPU	Single Module connect	Multi-Module connect
Modes of Operation	Manual Open Cap Analysis Mode(Operator presents sample to aspirationneedle)	Manual Open Cap Analysis Mode(Sample placed in tube holder position)
	Capillary Analysis ModeDilute sample 1:5	Pre-dilute Analysis ModeDilute sample 1:7

	Not AvailableHPC	Low WBC Mode (LWBC)Not Available
Parameters
Sample Aspiration/Fluidic Pathway	Two pathways	Single pathway
Software/Hardware	Not Available	Rules-based rerun/reflex
Throughput	Whole BloodApproximately 113-150 depending onmode used.	Whole Blood100 samples/hour maximumdepending on mode used.

	Body Fluid38 samples/hour	Body Fluid40 samples/hour maximum
Measuring Channels (seeSection 11 for detailedinformation on thesechannels)	WBC/BASO, DIFF, NRBCIMI	WNR, WDFWPC (Not available on XN-11)
	Not Available	PLT-F
Reagents	CELLPACK® (Diluent)CELLSHEATH™ (Diluent)NOT AVAILABLESTROMATOLYSER™-FB (Lyse)STROMATOLYSER™-4DL (Lyse)STROMATOLYSER™-4DS (Stain)STROMATOLYSER™-NR (Diluent)STROMATOLYSER™-NR (Stain)RET-SEARCH II (Diluent)RET-SEARCH II (Stain)STROMATOLYSER™- IM (Lyse)	CELLPACK® DCL (Diluent)CELLPACK™ DFL (Diluent)CELLSHEATH(C)™ (Diluent)Lysercell™ WNR (Lyse)Lysercell™ WDF (Lyse)Lysercell™ WPC* (Lyse)Fluorocell™ WNR (Stain)Fluorocell™ WDF (Stain)Fluorocell™ RET (Stain)Fluorocell™ PLT (Stain)Fluorocell™ WPC* (Stain)
		*Not used on XN-11 module.
Sample AspirationVolume	Sampler Mode – 200µLManual (Closed Cap) Mode - 200µLManual (Open Cap) Mode - 130µLCapillary Mode - 130µLBody Fluid Mode - 130µL	Sampler Mode - 88µLManual (Closed Cap) Mode - 88µLManual (Open Cap) Mode - 88µLDilution Mode - 70µLBody Fluid Mode - 88µL

11,

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Table 1: Substantial Equivalence - Similarities and Differences to the XN-Series Automated Hematology analyzers (Modules XN-11, XN-21) and XE-5000 Automated Hematology analyzer.

Sysmex XN-Series modules (XN-11, XN-21) Automated Hematology Analyzers 510(k) Submission

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Sysmex XN-Series modules (XN-11, XN-21) Automated Hematology Analyzers 510(k) Submission

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Sysmex XN-Series modules (XN-11, XN-21) Automated Hematology Analyzers 510(k) Submission

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.”