Predicate Devices

Reference Devices

Not Found

AI/ML (Artificial Intelligence / Machine Learning)

No
The summary describes a standard automated hematology analyzer using flow cytometry and data management for processing and reporting blood and body fluid parameters. There is no mention of AI, ML, or any related technologies in the device description, intended use, or performance studies. The data management unit appears to handle standard laboratory workflow and data processing, not AI/ML-driven analysis.

Therapeutic

No
Explanation: The device is an in-vitro diagnostic hematology analyzer used for screening and diagnosis, not for treating or preventing disease.

Diagnostic

Yes

The device is explicitly stated as "intended for in-vitro diagnostic use" in its "Intended Use / Indications for Use" section. It classifies and enumerates various blood and body fluid parameters, which are used to aid in the diagnosis of patient conditions.

SaMD (Software as a Medical Device)

No

The device description explicitly states that the Yumizen H2500 is an "analyzer unit" that "aspirate, dilute, mix, and analyze blood and body fluid samples." This involves physical manipulation and analysis of samples, indicating it is a hardware device with integrated software, not a software-only device.

IVD (In Vitro Diagnostic)

Yes, this device is an IVD (In Vitro Diagnostic).

Here's why:

Explicit Statement in Intended Use: The "Intended Use / Indications for Use" section clearly states: "The Yumizen H2500 is a quantitative multiparameter fully automated hematology analyzer intended for in-vitro diagnostic use in clinical laboratories by qualified healthcare professionals for the screening of patient populations."
Testing of Biological Specimens: The device is intended to perform tests on "Anticoagulated whole blood specimens" and "Body fluids (synovial fluids, serous fluids and cerebrospinal fluids)," which are biological specimens.
Quantitative Measurement of Parameters: The device classifies and enumerates various blood and body fluid parameters, providing quantitative results.
Use in Clinical Laboratories: The intended user and setting are "clinical laboratories by qualified healthcare professionals," which is a typical environment for IVD devices.
Screening of Patient Populations: The intended use includes "screening of patient populations," indicating a diagnostic purpose.

All of these points align with the definition of an In Vitro Diagnostic device, which is used to examine specimens derived from the human body to provide information for diagnostic purposes.

PCCP (Predetermined Change Control Plan) Authorized

N/A

Overview

Intended Use / Indications for Use

The Yumizen H2500 is a quantitative multiparameter fully automated hematology analyzer intended for in-vitro diagnostic use in clinical laboratories by qualified healthcare professionals for the screening of patient populations.

The Yumizen H2500 is intended to perform tests on the following specimens:

Anticoagulated whole blood specimens
Body fluids (synovial fluids, serous fluids and cerebrospinal fluids).

The Yumizen H2500 classifies and enumerates the following parameters:

A complete blood count (CBC) consisting of TNC, WBC, RBC, HGB, calculated HCT, MCV, calculated MCH, calculated MCHC, RDW-SD, RDW-CV, PLT, PLT-Ox, LPF, MPV.
A leukocyte differential count consisting of LYM (%#), MON (%#), NEU (%/#), EOS (%/#), BAS (%/#), IMG (%/#)
A nucleated red blood cell count consisting of NRBC (%/#).
A reticulocyte analysis consisting of RET (%/#), calculated CRC, IRF, RHCC.
Quantitative determination of blood cells in synovial fluids, serous fluids and cerebrospinal fluids consisting of BFWBC, BFRBC, BFPN (%/#), BFMN (%/#).

Note: Venous and capillary whole blood should be collected in K2EDTA anticoagulant. Serous and synovial fluids should be collected without anticoaqulant or in K2EDTA anticoagulant to prevent clotting of fluid. The use of anticoagulants with cerebrospinal fluid specimens is neither required nor recommended. Alternatively, Sodium Heparin or Lithium Heparin may be used for synovial fluid.

Product codes (comma separated list FDA assigned to the subject device)

GKZ

Device Description

The HORIBA Medical analyzer modules Yumizen H2500 are multi-parameter hematology analyzers intended to perform tests on whole blood samples collected in K2EDTA and body fluids (synovial and serous) collected in K2EDTA anticoaqulant. The analyzers can also perform tests on cerebrospinal fluids which should not be collected in any anticoaqulant.

The Analyzer Units (Yumizen H2500) aspirate, dilute, mix, and analyze blood and body fluid samples.

The Yumizen H2500 model provides Complete Blood Count (CBC), Differential (DIFF), Reticulocyte counts (RET) and Optical Platelet counts as well as Body Fluid counts (BF).

The analyzer models may function with:

a Data Management Unit (Yumizen P8000) which is the interface with the laboratory connections (LIS) and the Analyzer Unit(s). Through its interface, the Yumizen P8000 enables the user to monitor the workflow of patient data, centralize result data, perform reflex testing, customize rules, centralize the validation operations, run quality control, manage quality assurance on results.

Mentions image processing

Not Found

Mentions AI, DNN, or ML

Not Found

Input Imaging Modality

Not Found

Anatomical Site

Not Found

Indicated Patient Age Range

Adult and Pediatric

Intended User / Care Setting

Clinical laboratories by qualified healthcare professionals

Description of the training set, sample size, data source, and annotation protocol

Not Found

Description of the test set, sample size, data source, and annotation protocol

Summary of Performance Studies:

Precision/Reproducibility:
- Repeatability - Whole Blood: Four (4) test sites with seven (7) instruments. 116 residual K2EDTA whole blood samples (normal and contrived specimens for extremes of analytical measuring range). Each sample measured 12 consecutive times.
- Repeatability – Body Fluid: Four (4) test sites with seven (7) instruments. 87 residual body fluid samples (synovial, serous, and cerebrospinal fluids, normal and contrived specimens for extremes of analytical measuring range). Each sample measured 4 to 10 consecutive times.
- Reproducibility - Whole Blood: Four (4) test sites with four (4) instruments. Three (3) levels of ABX Difftrol and ABX Minotrol Retic whole blood control material. Each level run in duplicate twice a day for a minimum of 20 days.
- Reproducibility - Body Fluids: Four (4) test sites with four (4) instruments. Two (2) levels of BFTROL body fluid control material. Each level run in duplicate twice a day for a minimum of 20 days.
Linearity:
- Whole Blood: One (1) test site, two (2) instruments. For CBC: 2 instruments with 1 different reagent lot each. For RET and PLT-Ox: 2 instruments with 1 different reagent lot each. Minimum 7 concentration levels tested (1 below lower limit, at least 5 across range, 1 above upper limit). Each level tested in minimum 4 replicates on 2 instruments using 2 reagent lots.
- Body Fluids: One (1) test site, two (2) instruments, with one different reagent lot on each instrument. Minimum 7 concentration levels tested (1 below lower limit, at least 5 across range, 1 above upper limit). Each level tested in minimum 4 replicates on 2 instruments using 2 reagent lots.
Analytical Specificity/Interference:
- Interferences - Whole Blood: Four (4) test sites. Tested with two concentration levels for hemoglobin, triglycerides, bilirubin (total and direct), glucose, and yeast (Saccharomyces boulardii). Also evaluated intrinsic interferences (elevated RBCs, elevated PLTs, microcytic RBCs, fragile WBC, thrombocytosis, macrothrombocytosis, platelet aggregates, dual RBC population, RBC abnormal morphology, RBC fragments, RBC inclusions, RBC microcytosis, erythroblasts) using a subset of samples from method comparison study (minimum 17 specimens per interferent).
- Interferences - Body Fluids: Four (4) test sites. Tested with two concentration levels for hemoglobin, triglycerides, bilirubin (total and direct), total protein, and yeast (Saccharomyces boulardii). Also evaluated intrinsic interferences (mesothelial cells, malignant cells) using a subset of samples from method comparison study.
Stability:
- Whole Blood samples: Three (3) test sites. 14 whole venous blood K2EDTA specimens stored at ambient (20-24°C) and refrigerated (2-8°C) temperatures. Tested at regular intervals.
- Body Fluid samples: Two (2) test sites. 28 body fluid specimens (13 serous, 7 synovial, 8 cerebrospinal fluids) stored at ambient (20-24°C). Tested at regular intervals (serous/synovial at 6, 24, 27 hours; CSF at 3, 4, 4.5 hours).
Detection Limits (LoB, LoD, LoQ):
- Whole Blood: LoB/LoD for WBC, TNC, RBC, HGB, HCT, PLT, PLT-Ox, RET#. LoQ for WBC, TNC, RBC, HGB, HCT, PLT, PLT-Ox, RET#, RET%. Minimum 5 days for LoB, 3 days for LoD/LoQ. 6 blank samples for LoB, 6 low concentration whole blood samples for LoD, at least 4 low concentration samples for LoQ. Two (2) different reagent lots on different analyzers, each sample run 10 repeated times.
- Body Fluid: LoB/LoD/LoQ for BFWBC and BFRBC. Minimum 5 days for LoB, 3 days for LoD/LoQ. 6 blank samples for LoB, 6 low concentration body fluid samples for LoD, at least 4 low concentration samples for LoQ. Two (2) different reagent lots on different analyzers, each sample run 10 repeated times.
Carry-over:
- Whole Blood: One (1) test site, three (3) analyzers. High WBC, RBC, HGB, PLT, PLT-Ox, RET% and RET# samples assayed 3 consecutive times, followed by low target samples 3 consecutive times. Three sets of carry-over sequences run.
- Body Fluids: One (1) test site, three (3) analyzers. High BFWBC and BFRBC samples assayed 3 consecutive times, followed by low target samples 3 consecutive times. Three sets of carry-over sequences run.
Method Comparison with Predicate Device (Sysmex XN-Series, K112605):
- Whole Blood: Four (4) clinical sites (2 US, 2 European). 969 venous and/or capillary K2EDTA specimens from pediatric (21 years). Each sample analyzed on one Yumizen H2500 for all parameters.
- Whole Blood - Pediatric samples: Two (2) US clinical sites. At least 80 (approx. 40 male, 40 female) apparently healthy neonates, infants, children, adolescents (

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.”

Summary

0

Image /page/0/Picture/0 description: The image contains the logo of the U.S. Food and Drug Administration (FDA). On the left is the Department of Health & Human Services logo. To the right of that is the FDA logo, which is a blue square with the letters "FDA" in white. To the right of the blue square is the text "U.S. FOOD & DRUG ADMINISTRATION" in blue.

May 21, 2024

Horiba ABX Sas Caroline Ferrer Regulatory Affairs Manager Parc Euromedecine, Rue du Caducee BP7290 Montpellier Cedex 4, 34184 France

Re: K232946

Trade/Device Name: Yumizen H2500 Regulation Number: 21 CFR 864.5220 Regulation Name: Automated differential cell counter Regulatory Class: Class II Product Code: GKZ Dated: September 14, 2023 Received: September 20, 2023

Dear Caroline Ferrer:

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 (the 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. Although this letter refers to your product as a device, please be aware that some cleared products may instead be combination products. The 510(k) Premarket Notification Database available at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/pmn.cfm identifies combination product submissions. 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.

Additional information about changes that may require a new premarket notification are provided in the FDA guidance documents entitled "Deciding When to Submit a 510(k) for a Change to an Existing Device"

1

K232946 - Caroline Ferrer

(https://www.fda.gov/media/99812/download) and "Deciding When to Submit a 510(k) for a Software Change to an Existing Device" (https://www.fda.gov/media/99785/download).

Your device is also subject to, among other requirements, the Quality System (QS) regulation (21 CFR Part 820), which includes, but is not limited to, 21 CFR 820.30, Design controls; 21 CFR 820.90, Nonconforming product; and 21 CFR 820.100. Corrective and preventive action. Please note that regardless of whether a change requires premarket review, the QS regulation requires device manufacturers to review and approve changes to device design and production (21 CFR 820.30 and 21 CFR 820.70) and document changes and approvals in the device master record (21 CFR 820.181).

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 and Part 809); medical device reporting of medical device-related adverse events) (21 CFR Part 803) for devices or postmarketing safety reporting (21 CFR Part 4) for combination products (see https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safetyreporting-combination-products); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820) for devices or current good manufacturing practices (21 CFR Part 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR Parts 1000-1050.

Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to https://www.fda.gov/medical-device-safety/medical-device-reportingmdr-how-report-medical-device-problems.

For comprehensive regulatory information about mediation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/medicaldevices/device-advice-comprehensive-regulatory-assistance) and CDRH Learn (https://www.fda.gov/training-and-continuing-education/cdrh-learn). Additionally, you may contact the Division of Industry and Consumer Education (DICE) to ask a question about a specific regulatory topic. See the DICE website (https://www.fda.gov/medical-device-advice-comprehensive-regulatoryassistance/contact-us-division-industry-and-consumer-education-dice) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).

Sincerely,

Min Wu -

Min Wu, Ph.D. Branch Chief Division of Immunology and Hematology Devices OHT7: Office of In Vitro Diagnostics Office of Product Evaluation and Quality Center for Devices and Radiological Health

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Indications for Use

Device Name Yumizen H2500

Indications for Use (Describe)

The Yumizen H2500 is a quantitative multiparameter fully automated hematology analyzer intended for in-vitro diagnostic use in clinical laboratories by qualified healthcare professionals for the screening of patient populations.

The Yumizen H2500 is intended to perform tests on the following specimens:

· Anticoagulated whole blood specimens
· Body fluids (synovial fluids, serous fluids and cerebrospinal fluids).

The Yumizen H2500 classifies and enumerates the following parameters:

· A complete blood count (CBC) consisting of TNC, WBC, RBC, calculated HCT, MCV, calculated MCH, calculated MCHC, RDW-SD, RDW-CV, PLT, PLT-Ox, LPF, MPV.

· A leukocyte differential count consisting of LYM (%), NEU (%), EOS (%(#), BAS (%/#), IMG (%/#), IMG (%/#),
· A nucleated red blood cell count consisting of NRBC (%/#).
· A reticulocyte analysis consisting of RET (%/#), calculated CRC, IRF, RHCC.

· Quantitative determination of blood cells in synovial fluids, serous fluids and cerebrospinal fluids consisting of BFWBC, BFRBC, BFPN (%/#), BFMN (%/#).

Note: Venous and capillary whole blood be collected in K2EDTA anticoagulant. Serous and synovial fluids should be collected without anticoagulant or in K2EDTA anticoagulant to prevent clotting of fluid. The use of anticoagulants with cerebrospinal fluid specimens is neither required nor recommended. Alternatively, Sodium Heparin or Lithium Heparin may be used for synovial fluid.

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

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DO NOT SEND YOUR COMPLETED FORM TO THE PRA STAFF EMAIL ADDRESS BELOW.

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510(k) Safety and Effectiveness Summary

This summary of 510(k) safety and effectiveness information is being submitted in accordance with the requirements 21 CFR 807.92 (b)(3).

Submitted by:

Company: HORIBA ABX SAS Address: Parc Euromédecine Rue du Caducée – BP 7290 34184 Montpellier Cedex 4 FRANCE

Contact Person: Caroline FERRER Telephone (France): +33 467 141843 Email: caroline.ferrer@horiba.com

Date submitted: May 20th, 2024

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VOL 004 : 510(k) Safety and Effectiveness Summary

Yumizen H2500

Traditional 510(k): Supplement to Original Submission K232946

I.	BACKGROUND INFORMATION.............................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................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...........................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................
g.	Accuracy (Instrument):	32
h.	Carry-over:	32
B.	Comparison Studies	34
a.	Method Comparison with Predicate Device:	34
b.	Matrix Comparison:	39
c.	Clinical Sensitivity:	42
C.	Clinical Studies	43
D.	Clinical Cut-Off	43
E.	Expected Values/Reference Range:	44
F.	Other Supportive Instrument Performance Characteristics Data	46
VIII.	PROPOSED LABELING	46
IX.	CONCLUSION	46

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VOL 004 : 510(k) Safety and Effectiveness Summary Yumizen H2500 Traditional 510(k): Supplement to Original Submission K232946

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l. Background Information

A. 510(k) number

K232946

B. Applicant

HORIBA ABX SAS (Brand HORIBA Medical)

C. Proprietary and Established Names

Yumizen H2500

D. Regulatory Information

Product Code	Class	Regulation section	Regulation Description	Panel
GKZ	II	864.5220	Automated Differential Cell
Counter	Hematology

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Submission / Device Overview ll.

A. Purpose for Submission

Clearance for a new device: Yumizen H2500

B. Parameters

TNC, WBC, RBC, HGB, HCT, MCV, MCH, MCHC, RDW-SD, RDW-CV, PLT, MPV, LYM (%/#), MON (%/#), NEU (%/#), EOS (%/#), BAS (%/#), NRBC (%/#), BFWBC, BFRBC, BFPN (%/#), BFMN (%/#), PLT-Ox, LPF, RET (%/#), CRC, IRF, RHCC

C. Type of Test

A complete blood count (CBC)

A leukocyte differential count

A nucleated red blood cell count

A reticulocyte analysis

A body fluid count

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��. Intended Use/Indications for Use

A. Intended Use(s)

See Indications for Use below.

B. Indications for Use

The Yumizen H2500 is a quantitative multiparameter fully automated hematology analyzer intended for in-vitro diagnostic use in clinical laboratories by qualified healthcare professionals for the screening of patient populations.

The Yumizen H2500 is intended to perform tests on the following specimens:

Anticoagulated whole blood specimens ●
Body fluids (synovial fluids, serous fluids and cerebrospinal fluids). .

The Yumizen H2500 classifies and enumerates the following parameters:

A complete blood count (CBC) consisting of TNC, WBC, RBC, HGB, calculated . HCT, MCV, calculated MCH, calculated MCHC, RDW-SD, RDW-CV, PLT, PLT-Ox, LPF, MPV.
A leukocyte differential count consisting of LYM (%#), MON (%#), NEU (%/#), ● EOS (%/#), BAS (%/#), IMG (%/#)
A nucleated red blood cell count consisting of NRBC (%/#). ●
A reticulocyte analysis consisting of RET (%/#), calculated CRC, IRF, RHCC. ●
Quantitative determination of blood cells in synovial fluids, serous fluids and . cerebrospinal fluids consisting of BFWBC, BFRBC, BFPN (%/#), BFMN (%/#).

Note: Venous and capillary whole blood should be collected in K2EDTA anticoagulant. Serous and synovial fluids should be collected without anticoaqulant or in K2EDTA anticoagulant to prevent clotting of fluid. The use of anticoagulants with cerebrospinal fluid specimens is neither required nor recommended. Alternatively, Sodium Heparin or Lithium Heparin may be used for synovial fluid.

C. Special Conditions for Use Statement

Rx - For Prescription Use Only

9

IV. Device/System Characteristics

A. Device Description

The HORIBA Medical analyzer modules Yumizen H2500 are multi-parameter hematology analyzers intended to perform tests on whole blood samples collected in K2EDTA and body fluids (synovial and serous) collected in K2EDTA anticoaqulant. The analyzers can also perform tests on cerebrospinal fluids which should not be collected in any anticoaqulant.

The Analyzer Units (Yumizen H2500) aspirate, dilute, mix, and analyze blood and body fluid samples.

The Yumizen H2500 model provides Complete Blood Count (CBC), Differential (DIFF), Reticulocyte counts (RET) and Optical Platelet counts as well as Body Fluid counts (BF).

The analyzer models may function with:

· a Data Management Unit (Yumizen P8000) which is the interface with the laboratory connections (LIS) and the Analyzer Unit(s). Through its interface, the Yumizen P8000 enables the user to monitor the workflow of patient data, centralize result data, perform reflex testing, customize rules, centralize the validation operations, run quality control, manage quality assurance on results.

B. Principles of Operation

The HORIBA Yumizen H2500 uses impedance variation, optical and fluorescence flow cytometry, hydrodynamic focusing, and absorption spectrophotometry technologies to measure, count, and calculate hematological parameters in samples.

. Impedance variation consists in measuring the proportional response to the volume of the particle generated by its passage through a calibrated micro aperture concurrent with an electric current.
Optical and fluorescence flow cytometry is a process used to count and measure . the properties of cells or particles as they are carried by fluid through a sensing zone.

The cells are counted with impedance variation technology and physical and chemical characteristics of cells or particles are measured via light absorbency response from a light beam, or fluorescence response from a laser.

The Yumizen H2500 uses double hydrodynamic sequential system (DHSS) flow cytometry to focus and align cells into a single-file micro aperture through the sensing zone.

Two cell-free liguid sheaths surround the diluted sample and move with it in a laminar flow. The laminar flow prevents any mixing between the two liquid sheaths and the diluted sample.

Absorption spectrophotometry is based on the linear relationship between the ● amount of light that a well-mixed, nonflowing sample absorbs at a particular

10

absorption band and the concentration of an absorbing entity in the sample (Beer-Lambert Law).

To perform absorption spectrophotometry, the system uses the hemoglobin dilution as the sample and a specific reagent to release, oxidize and stabilize all heme iron from erythrocytes. The resulting complexes are quantified by spectrophotometry at a wavelength of 555nm.

Impedance variation technology through a calibrated micro aperture is used to analyse whole blood samples for RBC, PLT, TNC and body fluids samples (BFRBC). Flow cytometry technology is used to:

Separate NRBC from TNC to get the WBC and make the differential white blood ● cell formula with absorbency measurement.
Analyse whole blood samples for RET with fluorescence measurement.
. Analyse whole blood samples for PLT with absorbency measurement (PLT-Ox)
Analyse body fluids samples (BFWBC) ●

Absorption spectrophotometry is used to measure the HGB concentration.

All the other hematological parameters are calculated or derived from these different measurements.

Based on the available technologies and types of tests, the following analytical modes are available on the analyzers:

Analytical Modes	Corresponding tests
CBC	Complete blood count
DIF	Complete blood count
	Leukocyte differential count
DIF_LV	Complete blood count
	Leukocyte differential count for low values
RBC_PLTO	Complete blood count
	PLT-Ox
RET	Reticulocyte analysis
CBR (CBC + RET)	Complete blood count and
	Reticulocyte analysis
DIR (DIF + RET)	Complete blood count
	Leukocyte differential count
	Reticulocyte analysis
CBF	Body fluid count

Table 1 - Analvtical modes

11

C. Instrument Description

a. Instrument Name:

Yumizen H2500

b. Specimen Identification:

Tube sample ID can be identified manually using an external keyboard or the virtual keyboard or automatically using the integrated barcode reader or an external barcode reader.

c. Specimen Sampling and Handling:

The Yumizen H2500 operates in two sampling modes:

Automatic sampling (auto mixer and auto loader) .
Manual sampling (STAT mode) ●

d. Calibration:

Calibration is a procedure that is performed during specific situations such as installation, maintenance or service intervention. It ensures that the precision and accuracy of the analyzer are acceptable, so that accurate measurements are performed by the analyzer. Calibration is performed using materials with assigned values that are traceable to standard reference methods. It is recommended that the laboratory calibrate using ABX Minocal, which is a commercial whole blood calibrator.

e. Quality Control:

Quality control allows the user to monitor a set of analyses based on known sample values and ranges over a period of several months. Statistical computation performed on these populations allows the extraction of qualitative information related to the stability of the instrument.

The manufacturer's instructions are to be followed for material and frequency of quality control analysis.

Commercial controls:

ABX Difftrol, for CBC and Differential parameters ABX Minotrol Retic, for Retic parameters

BFTROL, for Body Fluid parameters

12

V. Substantial Equivalence Information

A. Predicate Device Name(s)

Sysmex XN-series

B. Predicate 510(k) Number(s)

K112605

C. Comparison with Predicate

Table 2 - Comparison with predicate

| Device & Predicate

Device(s)	Device Trade Name	K112605
	Yumizen H2500	Sysmex® XN-Series (XN-10, XN-20)
Automated Hematology Analyzers (K112605)
General Device Characteristics Similarities
Regulation	21 CFR 864.5220	21 CFR 864.5220
Product code	GKZ	GKZ
Intended
Use/Indications for
use	The Yumizen H2500 is a quantitative
multiparameter fully automated hematology
analyzer intended for in-vitro diagnostic use
in clinical laboratories by qualified
healthcare professionals for the screening
of patient populations.
The Yumizen H2500 is intended to perform
tests on the following specimens:
• Anticoagulated whole blood specimens
• Body fluids (synovial fluids, serous
fluids and cerebrospinal fluids).
The Yumizen H2500 classifies and
enumerates the following parameters:
• A complete blood count (CBC)
consisting of TNC, WBC, RBC, HGB,
calculated HCT, MCV, calculated MCH,
calculated MCHC, RDW-SD, RDW-CV,
PLT, PLT-Ox, LPF, MPV.
• A leukocyte differential count consisting
of LYM (%/#), MON (%/#), NEU (%/#),
EOS (%/#), BAS (%/#), IMG (%/#)
• A nucleated red blood cell count
consisting of NRBC (%/#).
• A reticulocyte analysis consisting of
RET (%/#), calculated CRC, IRF,
RHCC.
• Quantitative determination of blood cells
in synovial fluids, serous fluids and
cerebrospinal fluids consisting of
BFWBC, BFRBC, BFPN (%/#), BFMN	The Sysmex® XN-10 and XN-20 modules are
quantitative multi-parameter automated
hematology analyzers intended for in vitro
diagnostic use in screening patient populations
found in clinical laboratories. The XN-Series
modules classify and enumerate the following
parameters for whole blood: WBC, RBC, HGB,
HCT, MCV, MCH, MCHC, PLT (PLT-I, PLT-F),
NEUT%/#, LYMPH%/#, MONO%/#, EO%/#,
BASO%/#, NRBC%/#, IG%/#, RDW-CV, RDW-
SD, MPV, RET%/#, IRF, IPF, 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. Whole
blood should be collected in K2 or K3EDTA
anticoagulant and, Serous and Synovial fluids in
K2EDTA anticoagulant to prevent clotting of
fluid. The use of anticoagulants with CSF
specimens is neither required nor
recommended.
Device & Predicate
Device(s)		K112605
Device Trade Name	Yumizen H2500	Sysmex® XN-Series (XN-10, XN-20)
Automated Hematology Analyzers (K112605)
	(%/#).
	Note: Venous and capillary whole blood
should be collected in K2EDTA
anticoagulant. Serous and synovial fluids
should be collected without anticoagulant or
in K2EDTA anticoagulant to prevent clotting
of fluid. The use of anticoagulants with
cerebrospinal fluid specimens is neither
required nor recommended. Alternatively,
Sodium Heparin or Lithium Heparin may be
used for synovial fluid.
Test Principle
(same)	Performs hematology analyses according to
the Double Hydrodynamic Sequential
System, flow cytometry method (using a
semiconductor laser and fluorescent dyes)	Performs hematology analyses according to the
Hydro Dynamic Focusing (DC Detection), flow
cytometry method (using a semiconductor laser
and fluorescent dyes)
Test parameters*
(same)	WBC, RBC, HGB, HCT, MCV, MCH,
MCHC, PLT, NEU%/#, LYM%/#, MON%/#,
EOS%/#, BAS%/#, NRBC%/#, RDW-CV,
RDW-SD, MPV, RET%/#, IRF, IMG%/#,
BFWBC, BFRBC, BFMN%/#, BFPMN%/#	WBC, RBC, HGB, HCT, MCV, MCH, MCHC,
PLT (PLT-I), NEUT%/#, LYMPH%/#,
MONO%/#, EO%/#, BASO%/#, NRBC%/#,
RDW-CV, RDW-SD, MPV, RET%/#, IRF, IG%/#,
WBC-BF, RBC-BF, MN%/#, PMN%/#
Specimen types	Whole blood
Body fluid	Whole blood
Body fluid
Use of
Controls/Calibrators	Yes	Yes
Modes of Operation	Automatic Rack mode
Body Fluid Analysis Mode	Sampler Analysis Mode
Body Fluid Analysis Mode
	Manual mode (both close and open cap)
(Sample placed in tube holder position)	Manual Closed Analysis Mode
Manual Open Cap Analysis Mode (Sample
placed in tube holder position)
	Low Value mode (DIF_LV)	Low WBC Mode (LWBC)
Type of tubes	Venous and capillary tubes	Venous and capillary tubes
Patient population	Adult and Pediatric	General Patient population
Instrument operating
temperature	15 to 30°C	15 to 30°C
Relative humidity	Up to 85%	30 to 85%
Transportation
condition	From -20°C (-4°F) to +60°C (+140°F).	-10 to 60°C
	* Different names/formats of equivalent parameters are used between the Yumizen H2500 device and
Sysmex® XN-series; therefore, equivalent parameters are listed in the same order.

13

VOL 004 : 510(k) Safety and Effectiveness Summary Yumizen H2500 Traditional 510(k): Supplement to Original Submission K232946

14

VOL 004 : 510(k) Safety and Effectiveness Summary Yumizen H2500 Traditional 510(k): Supplement to Original Submission K232946

| Device & Predicate

Device(s)		K112605
Device Trade Name	Yumizen H2500	Sysmex® XN-Series (XN-10, XN-20)
Automated Hematology Analyzers (K112605)
General Device Characteristics - Differences
Test Principle
(different)	HGB: Spectrophotometry using cyanide-
free lysis	HGB: Spectrophotometry using SLS-hemoglobin
method
Test parameters
(different)	Whole blood parameters:
PLT-Ox, LPF, RHCC, CRC	Whole blood parameters:
PLT-F, IPF, RETHe#
	Body Fluid parameters:
/	Body Fluid parameters:
TC-BF
Reagents	ABX DILUENT 10L (Diluent)
ABX DILUENT 20L (Diluent)
ABX LYSEBIO 1L (Lyse)
ABX BASOLYSE 5L (Lyse)
NUCEDIFF 1L (Lyse)
ABX FLUOCYTE 0.5L (Stain)
ABX CLEANER 1L (Cleaner)
ABX MINOCLAIR 0.5L (Cleaner)	CELLPACKTM DCL (Diluent)
CELLPACKTM DFL (Diluent)
LYSERCELL WNR (Lyse)
LYSERCELL WDF (Lyse)
LYSERCELL WPC (Lyse)
SULFOLYSER (Lyse)
FLUOROCELL WNR (Stain)
FLUOROCELL WDF (Stain)
FLUOROCELL RET (Stain)
FLUOROCELL PLT (Stain)
FLUOROCELL WPC (Stain)
Controls / Calibrators	Whole Blood:
ABX DIFFTROL (3 Levels)
ABX MINOTROL RETIC (3 Levels)
ABX MINOCAL
Body Fluid:
BFTROL (2 Levels)	Whole Blood:
XN-Check - 3 Levels
XN CAL (XN-10/X-20 Calibrator)
XN CAL PF (Platelet F Calibrator)
Body Fluid:
XN Check BF - 2 Levels
Modes of Operation	No-predilute analysis mode
No dilution of sample	Pre-dilute Analysis Mode
Dilute sample 1 :7
Throughput	Whole Blood:
120 samples/hour maximum depending on
mode used.
Body Fluid
20 samples/hour maximum	Whole Blood
100 samples/hour maximum depending on
mode used.
Body Fluid
40 samples/hour maximum
Sample Aspiration
Volume	Rack analysis: 110 µL
Manual analysis: 110 µL	Sampler Mode – 88 µL
Manual (Closed Cap) Mode – 88 µL
Manual (Open Cap) Mode - 88 μL
Dilution Mode – 70 µL
Body Fluid Mode – 88 µL
Dimension	870(W) x 730(H) x 670(D) mm	645(W) x 855(H) x 755(D) mm
Weight	about 99 kg	about 78 kg (including the sampler)

15

VI. Standards/Guidance Documents Referenced

Table 3 - List of standards

Standard reference	Standard Title [FDA recognition number]
CLSI EP05-A3	Evaluation of Precision of Quantitative Measurement Procedures; Approved
Guideline - Third Edition [7-251]
CLSI EP06-A2	Evaluation of the Linearity of Quantitative Measurement Procedures [7-306]
CLSI EP07-A3	Interference Testing in Clinical Chemistry [7-275]
CLSI EP09-A3c	Measurement Procedure Comparison and Bias Estimation Using Patient
Samples [7-296]
CLSI EP17-A2	Evaluation of Detection Capability for Clinical Laboratory Measurement
Procedures; Approved Guideline - Second Edition [7-233]
CLSI EP28-A3c	Defining, Establishing, and Verifying Reference Intervals in the Clinical
Laboratory; Approved Guideline - Third Edition [7-224]
CLSI EP37-A	Supplemental Tables for Interference Testing in Clinical Chemistry [7-284]
CLSI H20-A2	Reference Leukocyte (WBC) Differential Count (Proportional) and Evaluation of
Instrumental Methods; Approved Standard - Second Edition [7-165]
CLSI H26-A2	Validation, Verification, and Quality Assurance of Automated Hematology
Analyzers; Proposed Standard - Second Edition [7-210]
CLSI H44-A2	Methods for Reticulocyte counting (Automated blood cell counters, Flow
cytometry, and Supravital dyes); Approved Guideline – Second edition
CLSI H56-A	Body Fluid Analysis for Cellular Composition; Approved Guideline. [7-163]
IEC 61010-1:2010+A1	Safety requirements for electrical equipment for measurement, control, and
laboratory use - Part 1: General requirements [19-34]
UL 61010-1:2012
R7.19	Standard for Safety for Electrical Equipment For Measurement, Control and
Laboratory Use; Part 1: General Requirements [19-41]
IEC 60601-1-2: 2014	Medical electrical equipment - Part 1-2: General requirements for basic safety
and essential performance - Collateral Standard: Electromagnetic disturbances

Requirements and tests [19-8] |
| IEC 60825-1: 2014 | Safety of laser products - Part 1: Equipment classification, and requirements |
| IEC 62304: 2015 | Medical device software - Software life cycle processes [13-79] |
| ISO 14971: 2019 | Medical devices - Application of risk management to medical devices [5-125] |
| ISO 15223-1: 2021 | Medical devices - Symbols to be used with information to be supplied by the
manufacturer - Part 1: General requirements [5-134] |
| Standard reference | Standard Title [FDA recognition number] |
| | |
| ISO 18113-3: 2022 | In vitro diagnostic medical devices - Information supplied by the manufacturer
(labelling) - Part 3: In vitro diagnostic instruments for professional use |

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17

Performance Characteristics (if/when applicable) VII.

A. Analytical Performance
a. Precision/Reproducibility:

Repeatability - Whole Blood

Repeatability studies were performed according to CLSI H26-A2 guide recommendations at four (4) test sites with seven (7) instruments using DIF, DIF, DIF LV, or RBC PLTO modes.

Within-run repeatability studies were performed using a total of 116 residual K2EDTA whole blood samples around medical decision levels and within the laboratory reference range. Contrived samples were utilized to cover the extremes of the analytical measuring range of some parameters.

Each sample was measured 12 consecutive times.

For each parameter, the mean and coefficient of variation (CV) were computed. All components of variation that were calculated met the pre-defined acceptance criteria. The results are summarized below.

| Target
Range | Recommended Target
Values | Parameter | N |-----------------|--------- | Normal | 4-10 109/L | Normal | 4-10 109/L | Normal | 3.6-6.2 1012/L | Normal | 12.0-18.0 g/dL | Normal | 36-54 % | Normal | 80-100 fL | Normal | 27-32 pg | Normal | 320-360 g/L | Normal | 5-17 % | Normal | 10-49 fL | Normal | 150-500 109/L | Normal | 8-12 fL | Normal | 150-500 109/L | Normal | 2-12 % | Normal | 25-50 % | Normal | 2-10 % | Normal | 45-80 % | Normal | 0.5-5 % | Normal | 0-2.5 % | Result Range | Max %CV | Max SD |
---------------------|-----------|----|--------------|---------|--------|
| WBC | 37 | 4.27-9.84 | 2 | 0.150 |
| TNC | 36 | 4.27-9.84 | 1.8 | 0.150 |
| RBC | 58 | 3.66-5.92 | 1.5 | 0.057 |
| HGB | 44 | 12.0-17.6 | 0.6 | 0.096 |
| HCT | 46 | 36.4-53.6 | 1.2 | 0.5 |
| MCV | 87 | 80.4-99.4 | 0.5 | 0.530 |
| MCH | 79 | 27.1-31.8 | 1.2 | 0.344 |
| MCHC | 84 | 320-355 | 1.2 | 3.954 |
| RDWcv | 71 | 12.6-16.9 | 2.7 | 0.350 |
| RDWsd | 53 | 31.4-48.9 | 3.4 | 1.453 |
| PLT | 64 | 156-479 | 5 | 11.595 |
| MPV | 83 | 8.2-12 | 3 | 0.242 |
| PLT-Ox | 16 | 155-469 | 4.7 | 12.317 |
| LPF | 15 | 2.1-11.2 | 20.7 | 0.834 |
| LYM% | 26 | 25.5-43.2 | 3.8 | 1.101 |
| MON% | 41 | 3.8-9.7 | 9.1 | 0.845 |
| NEU% | 36 | 46.8-79.2 | 1.9 | 1.093 |
| EOS% | 38 | 0.5-4.9 | 18.2 | 0.442 |
| BAS% | 75 | 0-2.2 | 39.3 | 0.370 |

Table 4 - Repeatability - Whole Blood normal samples

18

| Target
Range | Recommended Target
Values | Parameter | N | Result Range | Max %CV | Max SD |
|-----------------|------------------------------|-----------|----|--------------|---------|--------|
| Normal | 0.5-3 % | IMG% | 46 | 0.5-2.8 | 19.4 | 0.355 |
| Normal | 0.8-5 109/L | LYM# | 48 | 0.84-4.25 | 7.2 | 0.129 |
| Normal | 0.1-1 109/L | MON# | 42 | 0.33-0.98 | 9.1 | 0.058 |
| Normal | 2 - 8 109/L | NEU# | 36 | 2.18-7.32 | 2.6 | 0.113 |
| Normal | 0-0.5 109/L | EOS# | 44 | 0.02-0.48 | 22 | 0.027 |
| Normal | 0-0.25 109/L | BAS# | 73 | 0.00-0.21 | 38.4 | 0.053 |
| Normal | 0-0.2 109/L | IMG# | 48 | 0.01-0.19 | 11.6 | 0.039 |
| Normal | 0-2.5 % | NRBC% | 59 | 0.00-2.18 | 18.8 | 0.481 |
| Normal | 0-0.15 109/L | NRBC# | 54 | 0.00-0.02 | 0.0 | 0.017 |
| Normal | 0.5-3 % | RET% | 33 | 0.52-2.94 | 11.6 | 0.209 |
| Normal | 20-150 109/L | RET# | 35 | 28-147 | 17.1 | 12.525 |
| Normal | 0.75-3 % | CRC | 32 | 0.83-2.93 | 12.2 | 0.249 |
| Normal | 0.15-0.3 | IRF | 17 | 0.15-0.29 | 14.4 | 0.033 |
| Normal | 27-35 pg | RHCc | 21 | 28.41-34.86 | 3.5 | 1.077 |

VOL 004 : 510(k) Safety and Effectiveness Summary Yumizen H2500 Traditional 510(k): Supplement to Original Submission K232946

Table 5 - Repeatability – Whole Blood abnormal samples

| Target
Range | Recommended Target
Values | Parameter | N | Result Range | Max %CV | Max SD |
|-----------------|------------------------------|-----------|----|--------------|---------|--------|
| Low | 0.1-2 109/L | WBC | 1 | 0.81 | 3.9 | 0.032 |
| Low | 2-4 109/L | WBC | 4 | 2.81-3.97 | 1.8 | 0.065 |
| Low | 0.5-4 109/L | TNC | 5 | 0.81-3.97 | 3.9 | 0.065 |
| Low | 0.3-3.0 1012/L | RBC | 25 | 1.17-2.99 | 1.7 | 0.038 |
| Low | 3.0-3.6 1012/L | RBC | 23 | 3.02-3.56 | 0.9 | 0.028 |
| Low | 4.0 - 8.0 g/dL | HGB | 18 | 4.1-7.9 | 1.0 | 0.098 |
| Low | 8.0-12.0 g/dL | HGB | 43 | 8.0-11.8 | 0.9 | 0.121 |
| Low | 4-36 % | HCT | 59 | 9.8-35.6 | 1.6 | 0.4 |
| Low | 40-80 fL | MCV | 14 | 59.6-80.0 | 0.4 | 0.322 |
| Low | 30 -150 109/L | PLT | 9 | 56-130 | 8 | 7.236 |
| Low | 30 -150 109/L | PLT-Ox | 2 | 106-131 | 4.6 | 4.830 |
| Low | 10 - 25% | LYM% | 20 | 10.9-24.4 | 6 | 0.889 |
| Low | 20 - 45% | NEU% | 6 | 26.7-43.5 | 3.7 | 0.981 |
| Low | 0.00 - 0.15 | IRF | 18 | 0.03-0.15 | 25.6 | 0.031 |
| High | 10-30 109/L | WBC | 31 | 10.03-19.9 | 1.9 | 0.330 |
| High | 30-300 109/L | WBC | 5 | 34.4-150.73 | 1 | 0.966 |
| High | 10-300 109/L | TNC | 41 | 10.01-153.24 | 3.6 | 5.540 |
| High | 6.2-8 1012/L | RBC | 10 | 6.43-7.83 | 0.7 | 0.045 |

19

| Target
Range | Recommended Target
Values | Parameter | N | Result Range | Max %CV | Max SD |
|-----------------|------------------------------|-----------|----|--------------|---------|--------|
| High | 18.0-24.0 g/dL | HGB | 9 | 19.0-22.0 | 0.4 | 0.134 |
| High | 54-67 % | HCT | 10 | 54.1-65.7 | 0.8 | 0.5 |
| High | 100-200 fL | MCV | 13 | 101.7-137.7 | 0.5 | 0.531 |
| High | 17-50 % | RDWcv | 13 | 17.1-28.6 | 2.9 | 0.644 |
| High | 49-100 fL | RDWsd | 31 | 49.4-82.8 | 2.8 | 2.317 |
| High | 500-2500 109/L | PLT | 18 | 515-959 | 2 | 13.968 |
| High | 500-2500 109/L | PLT-Ox | 10 | 678-1047 | 2.3 | 23.649 |
| High | 12-100 % | LPF | 2 | 15.2-15.4 | 5.3 | 0.811 |
| High | 50-100 | LYM% | 2 | 54.6-58.8 | 1.3 | 0.735 |
| High | 10-100 | MON% | 15 | 10.1-20.5 | 5.6 | 0.903 |
| High | 80-100 | NEU% | 1 | 84.5-84.5 | 0.5 | 0.447 |
| High | 5-100 | EOS% | 5 | 6.4-22.7 | 4.9 | 0.770 |
| High | 2.5-100 | BAS% | 2 | 3.4-6 | 11.4 | 0.458 |
| High | 3-100 | IMG% | 7 | 3.6-26.8 | 16.1 | 1.272 |
| High | 5-300 109/L | LYM# | 2 | 5.2-6.85 | 2.6 | 0.136 |
| High | 1-300 109/L | MON# | 13 | 1.04-6.15 | 6 | 0.297 |
| High | 8-300 109/L | NEU# | 5 | 8.02-13.94 | 1.9 | 0.266 |
| High | 0.5-300 109/L | EOS# | 5 | 0.51-2.3 | 5.6 | 0.064 |
| High | 0.25-300 109/L | BAS# | 2 | 0.33-2.22 | 8 | 0.091 |
| High | 0.2-300 109/L | IMG# | 18 | 0.2-22.92 | 19.1 | 1.145 |
| High | 2.5-100 | NRBC% | 10 | 4.0-45.9 | 8.1 | 2.827 |
| High | 0.15-20 109/L | NRBC# | 14 | 0.16-6.03 | 17 | 0.414 |
| High | 3 - 35 % | RET% | 7 | 3.3-11.1 | 7.4 | 0.286 |
| High | 150-1200 109/L | RET# | 5 | 160-301 | 4.8 | 0.008 |
| High | 3 - 35 % | CRC | 5 | 3.2-6.7 | 4.7 | 0.235 |
| High | 0.3-1 | IRF | 4 | 0.31-0.39 | 8.3 | 0.026 |
| High | 35-100 ng | RHCc | 8 | 35.2-45.2 | 2.9 | 1.055 |

VOL 004 : 510(k) Safety and Effectiveness Summary Yumizen H2500 Traditional 510(k): Supplement to Original Submission K232946

Repeatability – Body Fluid

Repeatability studies were performed according to CLSI H56-A guide recommendations at four (4) test sites with seven (7) instruments using CBF mode.

Within-run repeatability studies were performed using a total of 87 residual body fluid samples (Synovial, Serous and Cerebrospinal Fluids) around medical decision levels and

20

within the laboratory reference range. Contrived samples were utilized to cover the extremes of the analytical measuring range of some parameters.

Each sample was measured 4 to 10 consecutive times.

For each parameter, the mean and coefficient of variation (CV) were computed. The data supports the validity of the repeatability performance claims for the instrument models tested, as summarized in Table below.

Table 6 - Repeatability – Body Fluid serous samples
Target
Range	Recommended Target
Values	Parameter	N	Result Range	Max %CV	Max SD
Level 1	5-100 106/L	BFWBC	8	0-29	10.4	8.5
Level 1	1500-5000 106/L	BFRBC	5	0-7597	17	500.8
Level 1	5-100 106/L	BFPN#	21	0-97	36.6	4.4
Level 1	5-25	BFPN%	21	0-7	39.7	3.6
Level 1	5-300v106/L	BFMN#	21	0-54	9.2	5.9
Level 1	5-80	BFMN%	14	0-4	11.7	3.6
Level 2	100-600 106/L	BFWBC	18	101-492	13.6	28.8
Level 2	5000-5000000 106/L	BFRBC	21	8445-775828	9.4	7596.8
Level 2	100-10000 106/L	BFPN#	11	110-3316	8.1	96.7
Level 2	25-100	BFPN%	8	25-85	15.4	6.7
Level 2	300-10000 106/L	BFMN#	17	322-2554	7.8	53.8
Level 2	80-100	BFMN%	24	81-99	4.4	3.7
Level 3	600-10000 106/L	BFWBC	12	699-3887	4.4	111.2

Table 6 - Repeatability – Body Fluid serous samples

Table 7 - Repeatability – Body Fluid synovial samples

| Target
Range | Recommended
Target Values | Parameter | N | Result Range | Max %CV | Max SD |
|-----------------|------------------------------|-----------|----|--------------|---------|---------|
| Level 1 | 5-100 106/L | BFWBC | 7 | 19-82 | 11.8 | 9.7 |
| Level 1 | 1500-5000 106/L | BFRBC | 2 | 1864-3440 | 18.1 | 482.2 |
| Level 1 | 5-100 106/L | BFPN# | 8 | 6-63 | 37.6 | 6.3 |
| Level 1 | 5-25 | BFPN% | 6 | 8-24 | 20.3 | 3.4 |
| Level 1 | 5-300 106/L | BFMN# | 11 | 9-236 | 20.6 | 7.7 |
| Level 1 | 5-80 | BFMN% | 17 | 13-79 | 17.6 | 3.6 |
| Level 2 | 100-600 106/L | BFWBC | 7 | 110-520 | 10.5 | 23.2 |
| Level 2 | 5000-5000000 106/L | BFRBC | 16 | 5084-3798731 | 8.7 | 30369.5 |
| Level 2 | 100-10000 106/L | BFPN# | 12 | 103-6179 | 8.8 | 213.2 |
| Level 2 | 25-100 | BFPN% | 15 | 34-87 | 9.8 | 5.4 |
| Level 2 | 300-10000 106/L | BFMN# | 11 | 484-6700 | 14.4 | 604.4 |
| Level 2 | 80-100 | BFMN% | 5 | 83-93 | 6.6 | 5.6 |
| Level 3 | 600-10000 106/L | BFWBC | 13 | 1144-9540 | 4.8 | 222.0 |

21

Table 8 - Repeatability – Body Fluid CSF samples
Target
Range	Recommended
Target Values	Parameter	N	Result Range	Max %CV	Max SD
Level 1	5-100 106/L	BFWBC	9	17-89	19.2	8.6
Level 1	1500-5000 106/L	BFRBC	3	2080-3678	16.0	357.2
Level 1	5-100 106/L	BFPN#	1	18	16.2	2.9
Level 1	5-25	BFPN%	2	6-8	0.0	0.0
Level 1	5-300 106/L	BFMN#	9	11-209	27.5	5.6
Level 1	5-80	BFMN%	4	5-45	18.2	3.5
Level 2	100-600 106/L	BFWBC	3	260-546	10.0	54.8
Level 2	5000-5000000 106/L	BFRBC	7	8555-2887945	7.0	11989.8
Level 2	100-10000 106/L	BFPN#	6	144-2929	14.7	65.8
Level 2	25-100	BFPN%	6	55-99	17.7	10.8
Level 2	300-10000 106/L	BFMN#	1	4387-4387	1.5	66.1
Level 2	80-100	BFMN%	4	84-97	9.3	7.8
Level 3	600-10000 106/L	BFWBC	3	640-4657	2.3	69.2

Table 8 - Re eatability Body Fluid CSF .

22

Reproducibility - Whole Blood

Reproducibility studies were performed to evaluate the within-run, between-run, between-day, between-instrument, and total precision of the Yumizen H2500 analyzer. Testing was performed using three (3) levels of each whole blood control material (ABX Difftrol and ABX Minotrol Retic). Each level was run in duplicate twice each day for a minimum of 20 days using a single calibration and reagent lot at each of the four (4) test sites. The results were analyzed in accordance with the CLSI EP05-A3 approved guideline and met the acceptance criteria. Results are summarized below.

Parameter	Level	N	Mean	Within run			Between run		Between day		Between site(a)		Total
				SD	CV%	SD	CV%	SD	CV%	SD	CV%	SD	CV%
WBC	L	320	2.28	0.04	1.60	0.01	0.35	0.00	0.00	0.07	3.22	0.08	3.62
10%L	N	320	7.28	0.06	0.83	0.06	0.80	0.00	0.00	0.19	2.66	0.21	2.90
	H	320	18.22	0.13	0.69	0.08	0.45	0.11	0.60	0.49	2.70	0.53	2.88
	L	320	2.41	0.02	0.78	0.01	0.34	0.00	0.00	0.02	0.64	0.03	1.07
RBC
1012/L	N	320	4.82	0.03	0.66	0.00	0.00	0.01	0.12	0.01	0.18	0.03	0.69
	H	320	5.54	0.04	0.76	0.00	0.00	0.01	0.20	0.04	0.63	0.06	1.01
	L	320	6.141	0.025	0.40	0.18	0.29	0.00	0.00	0.55	0.89	0.63	1.02
HGB
g/dL	N	320	13.679	0.041	0.30	0.000	0.00	0.022	0.16	0.113	0.83	0.122	0.89
	H	320	17.086	0.049	0.29	0.030	0.18	0.020	0.12	0.131	0.77	0144	0.84
	L	320	18.61	0.15	0.80	0.10	0.52	0.05	0.27	0.29	1.57	0.35	1.86
НСТ	N	320	41.02	0.31	0.74	0.08	0.19	0.08	0.20	0.56	1.35	0.92	1.57
%	H	320	51.44	0.42	0.82	0.00	0.00	0.16	0.30	0.80	1.56	0.90	1.78
	L	320	77.08	0.23	0.30	0.21	0.27	0.27	0.35	0.80	1.04	0.90	1.17
MCV	N	320	85.18	0.24	0.28	0.16	0.19	0.22	0.26	1.06	1.24	1.12	1.32
t	H	320	92.82	0.28	0.30	0.16	0.17	0.28	0.30	1.15	1.24	1.22	1.32
	L	320	25.42	0.21	0.84	0.10	0.41	0.00	0.00	0.38	1.48	0.44	1.75
MCH	N	320	28.40	0.19	0.68	0.03	0.09	0.00	0.00	0.26	0.91	0.32	1.14
ba	H	320	30.83	0.23	0.75	0.00	0.00	0.08	0.25	0.35	1.12	0.42	1.37
	L	320	329.87	2.74	0.83	2.05	0.62	0.85	0.26	8.23	2.50	8.96	2.72
MCHC	N	320	333.50	2.54	0.76	0.76	0.23	0.57	0.17	7.17	2.15	7.66	2.30
g/L	H	320	332.25	2.60	0.78	0.00	0.00	1.28	0.39	7.61	2.29	8.14	2.45
	L	320	15.93	0.25	1.57	0.05	0.33	0.04	0.23	0.29	1.83	0.39	2.45
RDW-CV
%	N	320	13.59	0.20	1.50	0.02	0.12	0.13	0.97	0.30	2.20	0.39	2.84
	H	320	12.34	0.20	1.58	0.10	0.82	0.09	0.73	0.27	2.16	0.36	2.90
RDW-SD	L	320	42.15	0.96	2.29	0.23	0.54	0.36	0.85	1.07	2.54	1.50	3.57
fr	N	320	39.79	0.78	1.96	0.33	0.83	0.61	1.54	0.93	2.34	1.40	3.51
	H	320	40.40	0.79	1.97	0.44	1.09	0.62	1.54	0.92	2.28	1.44	3.56
PLT	L	320	63.07	3.36	5.32	0.00	0.00	1.00	1.58	0.92	1.46	3.62	5.74
	N	320	247.03	6.45	2.61	0.00	0.00	1.61	0.65	7.27	2.95	9.86	3.99
10%L	H	320	483.15	8.15	1.69	2.53	0.52	0.00	0.00	14.94	3.09	17.21	3.56
	L	320	65.02	5.63	8.66	1.72	2.65	2.68	4.12	3.46	5.32	7.34	11.28
PLT-Ox	N	320	244.78	6.79	2.77	2.49	1.02	3.56	1.45	6.30	2.58	10.23	4.18
10%L	H	320	478.70	10.77	2.25	0.00	0.00	3.77	0.79	8.28	1.73	14.09	2.94
	L	320	11.17	0.17	1.53	0.06	0.54	0.04	0.39	0.07	0.59	0.20	1.77
MPV	N	320	10.66	0.09	0.81	0.03	0.32	0.03	0.27	0.10	0.96	0.14	1.32
EL	H	320	10.44	0.06	0.60	0.05	0.47	0.00	0.00	0.11	1.02	0.13	1.27
LPF	L	320	2.20	0.68	30.91	0.00	0.00	0.37	17.05	0.33	14.93	0.84	38.33
					Within run		Between run		Between day		Between site(a)		Total
Parameter	Level	N	Mean	SD	CV%	SD	CV%	SD	CV%	SD	CV%	SD	CV%
%	N	320	1.54	0.31	19.91	0.08	5.44	0.25	16.31	0.31	19.91	0.51	32.99
	H	320	1.36	0.21	15.38	0.09	6.45	0.17	12.51	0.25	18.09	0.37	27.61
LYM#
109/L	L	320	0.40	0.02	4.39	0.01	1.53	0.00	0.00	0.01	3.34	0.02	5.72
	N	320	1.33	0.03	2.16	0.01	0.83	0.00	0.00	0.04	3.10	0.05	3.87
	H	320	1.60	0.04	2.48	0.01	0.51	0.02	1.30	0.06	3.47	0.07	4.49
LYM%	L	320	17.52	0.85	4.83	0.00	0.00	0.16	0.89	0.20	1.12	0.88	5.04
	N	320	18.30	0.38	2.09	0.13	0.72	0.00	0.00	0.11	0.60	0.42	2.29
	H	320	8.80	0.23	2.57	0.07	0.76	0.02	0.26	0.07	0.78	0.25	2.81
MON#
109/L	L	320	0.15	0.01	9.16	0.01	6.08	0.00	0.00	0.01	3.89	0.02	11.67
	N	320	0.49	0.02	4.94	0.01	2.31	0.00	0.00	0.02	3.81	0.03	6.65
	H	320	0.82	0.04	5.28	0.03	3.39	0.00	0.00	0.04	4.87	0.07	7.95
MON%	L	320	6.67	0.60	9.05	0.41	6.13	0.00	0.00	0.18	2.76	0.75	11.28
	N	320	6.77	0.33	4.88	0.20	2.89	0.00	0.00	0.12	1.74	0.40	5.93
	H	320	4.49	0.23	5.16	0.16	3.63	0.00	0.00	0.17	3.81	0.33	7.37
NEU#
109/L	L	320	1.43	0.04	2.65	0.00	0.00	0.01	0.69	0.05	3.32	0.06	4.30
	N	320	4.67	0.06	1.21	0.05	1.12	0.00	0.00	0.12	2.52	0.14	3.02
	H	320	13.49	0.12	0.87	0.06	0.47	0.07	0.54	0.36	2.64	0.39	2.87
NEU%	L	320	62.91	0.99	1.57	0.49	0.77	0.23	0.37	0.00	0.00	1.13	1.79
	N	320	64.14	0.49	0.77	0.25	0.39	0.00	0.00	0.20	0.31	0.59	0.92
	H	320	74.06	0.36	0.48	0.09	0.12	0.00	0.00	0.19	0.25	0.41	0.56
EOS#
109/L	L	320	0.12	0.01	9.62	0.00	3.54	0.01	5.80	0.00	3.33	0.01	12.24
	N	320	0.23	0.02	8.04	0.01	2.33	0.00	0.00	0.00	1.28	0.02	8.47
	H	320	0.72	0.04	5.61	0.01	1.94	0.01	1.98	0.01	1.63	0.05	6.47
EOS%	L	320	5.28	0.49	9.36	0.18	3.34	0.29	5.58	0.18	3.42	0.63	11.90
	N	320	3.10	0.25	8.00	0.06	2.03	0.00	0.00	0.07	2.34	0.27	8.57
	H	320	3.93	0.23	5.73	0.04	0.98	0.05	1.39	0.05	1.19	0.24	6.10
BAS#
109/L	L	320	0.10	0.00	3.37	0.00	1.37	0.00	1.03	0.00	4.86	0.01	6.16
	N	320	0.32	0.00	1.46	0.00	1.02	0.00	0.77	0.01	4.00	0.01	4.45
	H	320	0.84	0.01	1.09	0.00	0.00	0.00	0.59	0.03	3.23	0.03	3.46
BAS%	L	320	4.37	0.06	1.44	0.03	0.70	0.05	1.19	0.10	2.19	0.13	2.97
	N	320	4.37	0.05	1.05	0.02	0.39	0.04	0.84	0.08	1.84	0.10	2.32
	H	320	4.58	0.04	0.82	0.00	0.00	0.01	0.25	0.03	0.76	0.05	1.15
NRBC#
109/L	L	320	0.17	0.01	4.63	0.00	1.75	0.00	0.00	0.01	3.32	0.01	5.96
	N	320	0.57	0.01	2.22	0.00	0.75	0.00	0.00	0.02	3.08	0.02	3.87
	H	320	0.69	0.02	2.48	0.00	0.70	0.01	1.28	0.02	3.47	0.03	4.51
NRBC%	L	320	7.50	0.36	4.84	0.00	0.00	0.07	0.99	0.08	1.12	0.38	5.06
	N	320	7.84	0.16	2.07	0.06	0.71	0.00	0.00	0.05	0.60	0.18	2.27
	H	320	3.77	0.10	2.75	0.00	0.00	0.00	0.00	0.03	0.70	0.11	2.84
IMG#
109/L	L	320	0.07	0.00	5.69	0.00	1.42	0.00	0.00	0.00	3.88	0.01	7.03
	N	320	0.24	0.00	1.65	0.00	1.22	0.00	0.09	0.01	2.48	0.01	3.22
	H	320	0.75	0.01	1.07	0.00	0.41	0.00	0.42	0.02	2.65	0.02	2.92
IMG%	L	320	3.25	0.08	2.51	0.04	1.15	0.00	0.00	0.01	0.41	0.09	2.79
	N	320	3.32	0.04	1.32	0.02	0.75	0.00	0.00	0.02	0.50	0.05	1.59
	H	320	4.14	0.04	1.08	0.00	0.03	0.00	0.00	0.02	0.54	0.05	1.21
TNC
109/L	L	320	2.45	0.04	1.49	0.01	0.49	0.00	0.00	0.08	3.20	0.09	3.57
	N	320	7.85	0.07	0.83	0.06	0.78	0.00	0.00	0.21	2.69	0.23	2.92
	H	320	18.91	0.13	0.68	0.08	0.44	0.12	0.63	0.52	2.73	0.55	2.91
					Within run		Between run		Between day		Between site(a)		Total
Parameter	Level	N	Mean	SD	CV%	SD	CV%	SD	CV%	SD	CV%	SD	CV%
RET#
109/L	1	320	65.31	4.40	6.73	1.63	2.50	0.30	0.45	2.20	3.36	5.19	7.94
RET#
109/L	2	320	180.31	6.26	3.47	2.70	1.50	1.34	0.74	0.85	0.47	7.00	3.88
RET#
109/L	3	320	355.78	8.31	2.34	3.59	1.01	2.92	0.82	0.75	0.21	9.54	2.68
RET%	1	320	1.86	0.12	6.69	0.05	2.45	0.00	0.00	0.07	3.60	0.15	7.99
RET%	2	320	5.14	0.17	3.40	0.07	1.40	0.04	0.85	0.04	0.69	0.20	3.84
RET%	3	320	10.04	0.23	2.31	0.10	0.95	0.07	0.68	0.04	0.39	0.26	2.62
CRC
[%]	1	320	1.18	0.08	6.72	0.03	2.54	0.01	0.45	0.05	3.90	0.10	8.19
CRC
[%]	2	320	3.21	0.11	3.47	0.05	1.49	0.03	0.94	0.05	1.55	0.13	4.19
CRC
[%]	3	320	6.23	0.15	2.34	0.06	0.98	0.05	0.85	0.10	1.55	0.19	3.09
IRF	1	320	0.31	0.02	7.70	0.01	4.09	0.00	0.00	0.01	2.15	0.03	8.98
IRF	2	320	0.48	0.01	3.12	0.01	2.11	0.00	0.00	0.03	5.61	0.03	6.75
IRF	3	320	0.53	0.01	1.74	0.01	2.26	0.00	0.00	0.03	5.70	0.03	6.37
RBC
1012/L	1	320	3.51	0.03	0.75	0.01	0.25	0.00	0.00	0.01	0.28	0.03	0.84
RBC
1012/L	2	320	3.51	0.02	0.63	0.01	0.42	0.00	0.00	0.01	0.39	0.03	0.85
RBC
1012/L	3	320	3.54	0.02	0.61	0.01	0.21	0.01	0.15	0.01	0.36	0.03	0.76
RHCC
pg	1	320	23.66	0.58	2.44	0.29	1.22	0.24	1.03	0.24	1.03	0.73	3.09
RHCC
pg	2	320	17.01	0.36	2.11	0.25	1.47	0.12	0.72	0.21	1.21	0.50	2.93
RHCC
pg	3	320	12.52	0.30	2.44	0.26	2.06	0.14	1.13	0.21	1.71	0.47	3.79

Table 9 - Reproducibility ABX Difftrol - combined sites analysis

HORIBA ABX SAS, FRANCE

VOL 004-20

23

VOL 004 : 510(k) Safety and Effectiveness Summary Yumizen H2500 Traditional 510(k): Supplement to Original Submission K232946

Control materials (ABX Diffrol, ABX Minotrol Retic and BFTROL) were analyzed at four sites using four instruments (one (a) instrument per site). Between site analysis corresponds to between instrument analysis.

24

VOL 004 : 510(k) Safety and Effectiveness Summary Yumizen H2500 Traditional 510(k): Supplement to Original Submission K232946

Table 10 - Reproducibility ABX Minotrol Retic - combined sites analysis

Control materials (ABX Diffrol, ABX Minotrol Retic and BFTROL) were analyzed at four sites using four instruments (one (a) instrument per site). Between site analysis corresponds to between instrument analysis.

Reproducibility - Body Fluids

Reproducibility studies were performed to evaluate the within-run, between-run, between-day, between-instrument, and total precision of the Yumizen H2500 analyzer. Testing was performed using two (2) levels of the body fluid control material (BFTROL). Each level was run in duplicate twice each day for a minimum of 20 days using a single calibration and reagent lot at each of the four (4) test sites. The results were analyzed in accordance with the CLSI EP05-A3 approved quideline and met the acceptance criteria. Results are summarized below.

Parameter	Level	N	Mean	Within run		Between run		Between day		Between site(a)		Total
				SD	CV%	SD	CV%	SD	CV%	SD	CV%	SD	CV%
BFRBC	2	320	77783	3258.20	4.19	0.00	0.00	0.00	0.00	2297.83	2.95	3986.96	5.13
BFRBC	3	320	522119	10520.51	2.01	816.66	0.16	1142.11	0.22	15093.99	2.89	18452.13	3.55
BFWBC	2	320	227	7.93	3.50	4.87	2.15	0.00	0.00	10.97	4.84	14.39	6.34
BFWBC	3	320	917	16.62	1.81	5.57	0.61	7.78	0.85	32.66	3.57	37.87	4.14
BFMN#	2	320	67	5.25	7.83	0.62	0.93	1.39	2.07	2.69	4.01	6.09	9.09
BFMN#	3	320	155	7.76	4.99	0.00	0.00	1.76	1.13	4.36	2.81	9.07	5.84
BFMN%	2	320	30	2.09	7.05	0.00	0.00	0.47	1.58	0.18	0.60	2.15	7.25
BFMN%	3	320	17	0.86	5.06	0.00	0.00	0.12	0.72	0.18	1.07	0.89	5.18

Table 11 - Reproducibility BFTROL - combined sites analysis

HORIBA ABX SAS, FRANCE

25

VOL 004 : 510(k) Safety and Effectiveness Summary Yumizen H2500 Traditional 510(k): Supplement to Original Submission K232946

Parameter	Level	N	Mean	Within run		Between run		Between day		Between site(a)		Total
				SD	CV%	SD	CV%	SD	CV%	SD	CV%	SD	CV%
BFPN#	2	320	160	7.35	4.60	3.26	2.04	0.00	0.00	8.24	5.16	11.51	7.21
BFPN#	3	320	761	16.14	2.12	7.48	0.98	5.69	0.75	28.45	3.75	34.04	4.48
BFPN%	2	320	70	2.09	2.96	0.00	0.00	0.47	0.66	0.18	0.25	2.15	3.05
BFPN%	3	320	83	0.86	1.03	0.00	0.00	0.12	0.15	0.18	0.22	0.89	1.06

Control materials (ABX Difftrol, ABX Minotrol Retic and BFTROL) were analyzed at four sites using four instruments (a) (one instrument per site). Between site analysis corresponds to between instrument analysis.

26

b. Linearity:

Linearity - Whole Blood

The study was performed according to CLSI EP06-A2 quide recommendations at one test site, using two (2) instruments:

For CBC parameters: two (2) Yumizen H2500 with one different reagent lot on . each instrument.
For RET and PLT-Ox parameters, two (2) Yumizen H2500 with one different ● reagent lot on each instrument

For each parameter, the linearity range (commercial or prepared from dilutions of samples) using a minimum of seven (7) concentration levels was analyzed:

. One (1) sample underneath the lower limit of the linearity interval
At least five (5) samples with concentrations over the entire linearity range .
One (1) sample over the upper limit of the linearity interval .

Each level is tested in a minimum of four (4) replicates on two (2) instruments using two (2) reagent lots.

Results are presented in the table below. All results met the predefined acceptance criteria and were determined to be acceptable.

Parameter	Unit	Linearity range
WBC	$10^9/L$
( $10^3/\mu L$ )	0.06 – 344.50
TNC	$10^9/L$
( $10^3/\mu L$ )	0.06 – 344.50
RBC	$10^{12}/L$
( $10^6/\mu L$ )	0.17-8.63
HGB	g/dL	0.5 – 25.8
HCT	%	1.5 – 72.7
PLT	$10^9/L$
( $10^3/\mu L$ )	5 – 2706
PLT-Ox	$10^9/L$
( $10^3/\mu L$ )	7 – 2570
RET#	$10^9/L$	8 – 1276
NRBC#	$10^9/L$	0.00 – 21.21

Table 12 - Whole Blood linearity summary

27

Linearity - Body Fluids

The study was performed according to CLSI EP06-A2 guide recommendations at one test site, using two (2) instruments, with one different reagent lot on each instrument.

For each parameter, the linearity range (prepared from dilutions of samples) using a minimum of seven (7) concentration levels was analyzed:

One (1) sample underneath the lower limit of the linearity interval .
At least five (5) samples with concentrations over the entire linearity range ●
One (1) sample over the upper limit of the linearity interval ●

Each level is tested in a minimum of four (4) replicates on two (2) instruments using two (2) reagent lots.

Results are presented in the table below. All results met the predefined acceptance criteria and were determined to be acceptable.

Parameters	Unit	Linearity range
BFWBC	106/L	3 – 11 345
BFRBC	106/L	1079 – 5 394 633

Table 13 - Body Fluid linearity summary

c. Analytical Specificity/Interference:

Interferences - Whole Blood

The susceptibility of the Yumizen H2500 device to interference in the presence of hemoglobin, triglycerides, bilirubin, cholesterol, elevated RBCs, elevated RBCs, elevated PLTs, microcytic RBCs and other potential interferents was tested in whole blood samples collected in K2EDTA tubes, at four (4) test sites.

Hemoglobin, Lipemia, Bilirubin, Glucose and Yeast

For the Hemoglobin, Lipemia, Bilirubin, Glucose and Yeast studies, interferent levels were tested with samples at two concentration levels, according to CLSI EP7-A3 quidelines.

The potential interfering substance is added to a sample and the bias relative to a control portion of the sample is evaluated ("paired-difference testing"). This bias was compared to the acceptance criteria.

The following parameters were evaluated for each potential interferent:

28

Table 14 - Whole Blood Parameters - Potential Interferences
Parameters	Potential interferent
WBC, HGB, LYM#, MON#, NEU#, EOS#,
RET#	Hemoglobin
WBC, LYM#, MON#, NEU#, EOS#, HGB,
PLT, PLT-Ox	Lipemia (Triglycerides or Cholesterol)
HGB, PLT, PLT-Ox, MPV	Bilirubin (Total and Direct)
MCV	Glucose
PLT, PLT-Ox, MPV	Yeast

Whole Blood Parameters Potential Interferents

The Yumizen H2500 device were considered not susceptible to interference from Hemoglobin, Lipemia. Bilirubin, Glucose and Yeast, if the absolute difference or % difference criteria were met for each measurand.

Whole Blood Intrinsic Interferences

A study was conducted to evaluate the susceptibility of the Yumizen H2500 device to interference from Intrinsic Interferences in native whole blood specimens, according to CLSI H26-A2 guidelines.

This study utilized a subset of samples tested in the method comparison study, in four (4) test sites. where unique, native whole blood specimens collected in K2EDTA tubes were identified with potential interference analysis. A minimum of 17 specimens were evaluated per interferent.

The Yumizen H2500 device results for a parameter were considered not susceptible to interference from an interferent condition if the visual inspection of the difference plot does not differentiate the two groups (with and without interferent). The visual inspection was used for this analysis because the study compares the Yumizen H2500 device and another method (Sysmex XN-10) in specimens with the interfering condition. Overall, the Yumizen H2500 device demonstrated no interference in measuring WBC, RBC, PLT, MCV, and HGB from elevated WBC, RBC, and PLT measurands in native whole blood specimens.

Interferent	Level	Conclusion
Hemoglobin	1.4 g/dL	No interference was detected on WBC,
HGB, Differential and RET parameters.
Lipemia	Cholesterol 453.6 mg/dL
and/or
Triglycerides 2621.7 mg/dL	No significant effect was detected on WBC
and Differential, HGB, MCH, MCHC, PLT,
PLT-Ox and MPV parameters.
Total Bilirubin	60 mg/dL	No interference was detected with total
bilirubin on HGB, MCH, MCHC, PLT, PLT-
Ox, MPV parameters.
Direct Bilirubin
(Conjugated)	19 mg/dL	Conjugated bilirubin has a significant
effect on low HGB level (4 g/dL).
No interference was detected with
conjugated bilirubin on MCH, MCHC, PLT,
Interferent	Level	Conclusion
Glucose	960 mg/dL	PLT-Ox, MPV parameters.
No interference detected on MCV, RDW-CV and RDW-SD parameters.
Yeast
(Saccharomyces boulardii)	50 mg/L	No interference was detected on PLT, PLT-Ox, MPV parameters.
Leukocytosis
(Elevated WBCs)	>32 109/L WBC

59 109/L WBC
300 109/L | Significant effect on low MCV
Significant effect on high MCV
No interference detected on RBC, HGB, MCH, MCHC, RDW-CV, RDW-SD, PLT, PLT-Ox, MPV and NRBC parameters. |
| Fragile WBC | - | No interference was detected. |
| Thrombocytosis
(Elevated Platelets) | PLT>600 109/L | No interference detected on WBC, WBC Differential, RBC, HGB, HCT, MCV, RDW-CV, RDW-SD, MPV parameters. |
| Macrothrombocytosis | - | PLT-Ox and LYM# potentially increased.
No interference detected on WBC/WBC differential, RBC, HGB, HCT, MCV, MCH, MCHC, RDW-CV, RDW-SD, PLT, MPV, NRBC, RET parameters. |
| Platelet Aggregates | - | PLT, PLT-Ox and LYM# potentially impacted.
No interference was detected on WBC/WBC differential, MPV, NRBC and RET. |
| Dual RBC population | - | RDW-SD potentially impacted.
No interference detected on RBC, HCT, MCV, MCH, MCHC, RDW-CV parameters. |
| RBC abnormal morphology | - | MCV, RDW-SD, PLT-Ox and MPV potentially impacted.
No interference detected on RBC, HGB, HCT, RDW-CV and RET parameters. |
| RBC Fragments
(schiztocytes) | - | PLT-Ox and RET potentially impacted.
No interference detected on PLT, MPV and RET parameters. |
| RBC inclusions | - | PLT-Ox potentially impacted.
No interference detected on RBC, HCT, MCV, MCH, MCHC, RDW-CV parameters. |
| RBC Microcytosis | MCV10% | WBC and Differential potentially impacted.
No interference detected on RET parameter. |

Table 15 - Potential interferent study summary

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Interferences - Body Fluids

The susceptibility of the Yumizen H2500 device to interference in the presence of hemoglobin, triglycerides, bilirubin, total protein, mesothelial cells, and other interferents was tested in body fluid samples collected in K2EDTA tubes, at four (4) test sites.

Hemoglobin, Lipemia, Bilirubin, Total Protein and Yeast

For the Hemoglobin, Lipemia, Bilirubin, Total Protein and Yeast studies, interferent levels were tested with samples at two concentration levels, according to CLSI EPT-A3 auidelines.

The potential interfering substance is added to a sample and the bias relative to a control portion of the sample is evaluated ("paired-difference testing"). This bias was compared to the acceptance criteria.

The following parameters were evaluated for each potential interferent:

Parameters	Potential interferent
BFWBC, BFRBC	Hemoglobin
BFWBC, BFRBC	Lipemia (Triglycerides)
BFWBC, BFRBC	Bilirubin (Total and Direct)
BFWBC, BFRBC	Total protein
BFWBC	Yeast

Table 16 - Whole Blood Parameters - Potential Interferents

The Yumizen H2500 device were considered not susceptible to interference from Hemoglobin, Lipemia, Bilirubin and Total Protein, if the absolute difference or % difference criteria were met for each measurand.

Interference from yeast was detected.

Body Fluid Intrinsic Interferences

A study was conducted to evaluate the susceptibility of the Yumizen H2500 device to interference from Intrinsic Interferences in native body fluid specimens, according to CLSI H26-A2 guidelines.

This study utilized a subset of samples tested in the method comparison study, in four (4) test sites, where unique, native body fluid specimens were identified with potential interferents for interference analysis.

The Yumizen H2500 device results for a parameter were considered not susceptible to interference from an interferent condition if the visual inspection of the difference plot does not differentiate the two groups (with and without interferent). The visual inspection was used for this analysis because the study compares the Yumizen H2500 device and another method (Sysmex XN-10) in specimens with the interfering condition. Overall, the Yumizen H2500 device demonstrated no interference in measuring BFWBC and BFRBC from presence of mesothelial cells or malignant cells in native body fluid specimens.

31

Interferences from the presence of crystals or liposomal particles on BFWBC is well described in literature.

Interferent	Level	Conclusion
Hemoglobin	2 g/dL	No significant effect was detected on
BFWBC, BFRBC on three (3) types of
body fluids.
Lipemia	Triglycerides 1593 mg/dL	No significant effect was detected on
BFWBC, BFRBC on serous fluids.
Total Bilirubin	25.9 mg/dL	No significant effect was detected on
BFWBC, BFRBC on serous fluids.
Direct Bilirubin
(Conjugated)	39.3 mg/dL	No significant effect was detected on
BFWBC, BFRBC on serous fluids.
Total Protein	50 mg/L	No interference detected on BFWBC,
BFRBC parameters on all three (3) types
of body fluids.
Yeast
(Saccharomyces boulardii)	50 mg/dL	Significant effect was detected on BFWBC
on all three (3) types of body fluids.
Crystals	-	This interference is known and
documented in bibliography: crystals may
interfere with BFWBC and generate a
pollution on the scattergram.
Mesothelial cells	-	No interference detected with mesothelial
cells on native serous fluids.
Malignant cells	-	No interference detected with mesothelial
cells on native serous and CSF fluids.
Liposomal particles	-	This interference is known and
documented in bibliography: liposomal
particles may interfere with BFWBC and
generate a pollution on the scattergram.

d. Traceability, Stability, Expected Values:

Stability - Whole Blood samples:

A total of 14 whole venous blood specimens (collected in K2EDTA) were analyzed on the Yumizen H2500 at three (3) test sites. Following the collection (T0), each specimen was divided in half, with one sample stored at ambient temperature (20-24°C) and the other stored under refrigerated conditions (2-8℃). Testing for stability was performed at regular intervals after (TO) When sufficient volume is available, each time point is tested in duplicate.

Acceptance criteria for each parameter was established for defined time intervals at each storage condition as the difference between the recovery of the parameter at defined time points and time point zero (TO). The acceptance criteria were met for each claimed storage conditions:

32

Table 18 - Whole Blood - Sample stability Study results
	Room temperature	Refrigerated temperature
WHOLE BLOOD	24h for CBC/LMNE/NRBC/
RET parameters	48h for CBC/LMNE/NRBC parameters
72h for RET parameters

Sample stability study results Whole Blood -

Stability - Body Fluid samples:

28 body fluid specimens (13 serous, 7 synovial, and 8 cerebrospinal fluids) were analyzed on the analyzer at two (2) test sites. Following the collection (TO), each specimen was stored at ambient temperature (20-24°C). For serous and synovial fluids, testing for stability was performed at 6, 24 and 27 hours after (TO), and for cerebrospinal fluids, testing for stability was performed at three (3), four (4) and 4.5 hours after (TO). The acceptance criteria for sample stability is given as an acceptable maximum bias of the value at T with the value at (T0).

	Table 19 – Body Fluid - Sample stability study results
--	--------------------------------------------------------	--

	Room temperature
Serous fluids	24h for BFWBC/BFRBC/BFPN/BFMN parameters
Synovial fluids	24h for BFWBC/BFRBC/BFPN/BFMN parameters
CSF	4h for BFWBC/BFRBC/BFPN/BFMN parameters

Per established literature, body fluid samples should be stored at room temperature and analyzed within 1 hour of collection.

e. Detection Limits:

Limit of Blank - Whole Blood

The Limit of Blank (LoB) for WBC, TNC, RBC, HGB, HCT, PLT, PLT-Ox and RET# was determined according to CLSI EP17-A2 guide recommendations. Testing was conducted over a minimum of five (5) days using six (6) blank samples, with two (2) different reagent lots on different analyzers, each sample being run 10 repeated times. The results obtained from all samples were used to calculate the LoB for each parameter.

33

Limit of Detection - Whole Blood

The Limit of Detection (LoD) for WBC, TNC, RBC, HGB, HCT, PLT, PLT-Ox and RET# was determined according to CLSI EP17-A2 quide recommendations. Testing was conducted over a minimum of three (3) days using six (6) low concentration whole blood samples, with two (2) different reagent lots on different analyzers, each sample being run 10 repeated times. The results obtained from all samples were used to calculate the LoD for each parameter.

Limit of Quantitation - Whole Blood

The Limit of Quantitation (LoQ) for WBC, TNC, RBC, HGB, HCT, PLT, PLT-Ox, RET# and RET% was determined according to CLSI EP17-A2 quide recommendations. Testing was conducted over a minimum of three (3) days using at least four (4) low concentration whole blood samples, with two (2) different reagent lots on different analyzers, each sample being run 10 repeated times. The results obtained from all samples were used to calculate the Mean, Total error, and LoQ for each parameter. All results met the predefined acceptance criteria and were determined to be acceptable.

Parameter	Unit	LoB	LoD	LoQ
WBC	109/L
(103/μL)	0.05	0.07	0.10
TNC	109/L
(103/μL)	0.05	0.07	0.10
RBC	1012/L
(106/µL)	0.01	0.05	0.20
HGB	g/dL	0.1	0.3	0.8
HCT	%	0.1	0.3	2
PLT	109/L
(103/μL)	2	4	7
PLT-Ox	109/L
(103/μL)	2	6	10
RET#	109/L
(103/μL)	2	7	10

Table 20 - Whole Blood - Analytical Sensitivity Summary

Not applicable, ratio result

Limit of Blank - Body Fluid

The Limit of Blank (LoB) for BFWBC and BFRBC was determined according to CLSI EP17-A2 quide recommendations. Testing was conducted over a minimum of five (5) days using six (6) blank samples, with two (2) different reagent lots on different analyzers, each sample being run 10 repeated times. The results obtained from all samples were used to calculate the LoB for each parameter.

34

Limit of Detection - Body Fluid

The Limit of Detection (LoD) for BFWBC and BFRBC was determined according to CLSI EP17-A2 guide recommendations. Testing was conducted over a minimum of three (3) days using six (6) low concentration body fluid samples, with two (2) different reagent lots on different analyzers, each sample being run 10 repeated times. The results obtained from all samples were used to calculate the LoD for each parameter.

Limit of Quantitation - Body Fluid

The Limit of Quantitation (LoQ) for BFWBC and BFRBC was determined according to CLSI EP17-A2 guide recommendations. Testing was conducted over a minimum of three (3) days using at least four (4) low concentration body fluid samples, with two (2) different reagent lots on different analyzers, each sample being run 10 repeated times. The results obtained from all samples were used to calculate the Mean, Total error, and LoQ for each parameter. All results met the predefined acceptance criteria and were determined to be acceptable.

Parameter	Unit	LoB	LoD	LoQ
BFWBC	106/L	2	4	5
BFRBC	106/L	500	1000	1500

Table 21 - Body Fluids - Analytical Sensitivity Summary

f. Assay Cut-Off:

Not applicable

q. Accuracy (Instrument):

Not applicable

h. Carry-over:

Carry-over - Whole Blood

Carryover was evaluated by assaying whole blood K2EDTA samples with high WBC, RBC, HGB, PLT, PLT-Ox, RET% and RET# counts three consecutive times (high 1, high 2, high 3) followed immediately by testing samples with low target values consecutively three times (low 4, low 5, low 6) in accordance with CLSI H26-A2 guide. Three sets of carry-over sequences were run for each parameter on three analyzers at one (1) test site.

The percentage of carryover is calculated using the formula below:

35

low 4 – low 6 Ct % = × 100 high 3 – low 6

Where:

is the first low sample analyzed after the high sample runs low 4:

is the last low sample analyzed after the high sample runs low 6:

high 3: is the last high sample analyzed

All carry-over results are within specifications for the Yumizen H2500 systems.

Carry-over - Body Fluids

Carryover was evaluated by assaving body fluid samples (serous and synovials) with high BFWBC and BFRBC counts three consecutive times (high 1, high 2, high 3) followed immediately by testing samples with low target values consecutively three times (low 4, low 5, low 6) in accordance with CLSI H26-A2 quide. Three sets of carry-over sequences were run for each parameter on three analyzers at one (1) test site.

The percentage of carryover is calculated using the formula below:

low 4 – low 6 Ct % = high 3 – low 6

Where:

low 4: is the first low sample analyzed after the high sample runs

is the last low sample analyzed after the high sample runs low 6:
high 3: is the last high sample analyzed

All carry-over results are within specifications for the Yumizen H2500 systems.

36

B. Comparison Studies

a. Method Comparison with Predicate Device:

Method comparison studies were conducted to assess the performance of the Yumizen H2500 device, compared to the predicate device (Sysmex XN-Series, XN-10, K112605), according to EP9-A3 quidelines.

Whole Blood

A method comparison study was conducted to assess the performance of the Yumizen H2500 device when compared to the predicate device, Sysmex XN-Series (XN-10, XN-20) (K112605). A total of 969 venous and/or capillary specimens collected in K2EDTA from pediatric (≤21 years) and adult subjects including a wide variety of disease states (clinical conditions) were tested across four (4) clinical sites (two (2) US sites and two (2) European sites).

Venous and/or capillary whole blood leftover specimens were collected in K2EDTA tubes from a wide range of demographics (age and sex) and disease states (clinical conditions). In total, there were 143 specimens collected from subjects with one or more known medical conditions. Study sites aimed to cover the target assay reportable range for the parameters. A maximum of 10% samples were permitted to be contrived to cover the entire target assay reportable range.

Each specimen was tested within six (6) hours from the time of collection in two (2) replicates on the Yumizen H2500 and one (1) replicate on the Sysmex XN-10 System, when sufficient volume was available. Specimens were tested on the Yumizen H2500 and the Sysmex XN-Series (XN-10, XN-20) within three (3) hours of each other.

A Passing-Bablok regression analysis was performed. Bias at medical decision points were also evaluated for all sites combined. All results were within the predefined acceptance criteria and found to be acceptable. Overall, the Yumizen H2500 demonstrated comparable performance to the predicate device, Sysmex XN-Series (XN-10, XN-20) (K112605) in an intended use population in a clinical laboratory setting.

37

A summary of the results is presented in the table below:

| Parameter
(unit) | N | Sample Range | r
(95% CI) | Slope
(95% CI) | Intercept
(95% CI) |
|-------------------------------|-----|----------------|------------------------|--------------------------|------------------------------|
| WBC (109/L)
(103/μL) | 936 | 0.19 - 232 | 0.996
[0.996;0.997] | 1.012
[1.007 ; 1.017] | 0.045
[0.014 ; 0.076] |
| TNC (109/L)
(103/μL) | 937 | 0.19 - 232 | 0.996
[0.996;0.997] | 1.006
[1.00 ; 1.01] | 0.080
[0.05 ; 0.11] |
| RBC (1012/L)
(106/μL) | 941 | 0.54 - 7.31 | 0.997
[0.997;0.998] | 1.006
[1.00 ; 1.01] | -0.017
[-0.03 ; 0.01] |
| HGB (g/dL) | 941 | 2 - 22.1 | 0.998
[0.998;0.998] | 1.000
[1 ; 1] | 0.000
[0 ; 0] |
| HCT (%) | 941 | 5.8 - 65.3 | 0.985
[0.983;0.987] | 1.036
[1.024 ; 1.048] | -1.4
[-1.9 ; -1.0] |
| MCV (fL) | 940 | 60.6 - 140 | 0.893
[0.88;0.906] | 1.015
[0.983 ; 1.052] | -2.119
[-5.381 ; 0.804] |
| MCH (pg) | 940 | 18.6 - 46.1 | 0.976
[0.973;0.979] | 1.000
[1.000 ; 1.022] | 0.000
[-0.662 ; 0.000] |
| MCHC (g/L) | 940 | 278 - 379 | 0.184
[0.106;0.238] | 0.545
[0.5 ; 0.6] | 149.500
[132.0 ; 164.5] |
| RDW-CV (%) | 924 | 10.7 - 30.4 | 0.872
[0.857;0.888] | 0.868
[0.833 ; 0.901] | 2.316
[1.860 ; 2.843] |
| PLT (109/L)
(103/µL) | 939 | 9 - 1780 | 0.995
[0.995;0.996] | 0.977
[0.970 ; 0.984] | 2.841
[1.447 ; 3.996] |
| PLT-Ox
(109/L)
(103/µL) | 801 | 10 - 1780 | 0.988
[0.986;0.99] | 0.962
[0.949 ; 0.974] | 3.570
[1.503 ; 5.583] |
| LPF (%) | 791 | 0.4 - 40.9 | 0.872
[0.856;0.889] | 0.833
[0.786 ; 0.888] | 0.067
[-0.100 ; 0.222] |
| MPV (fL) | 877 | 7.2 - 13.3 | 0.901
[0.888;0.913] | 1.000
[0.976 ; 1.000] | -1.000
[-1.000 ; -0.763] |
| NRBC% (%) | 930 | 0 - 66.7 | 0.927
[0.918;0.936] | 0.609
[0.455 ; 0.73] | 0.000
[0.000 ; 0.000] |
| NRBC#
(109/L)
(103/μL) | 930 | 0.00 - 9.08 | 0.951
[0.945;0.957] | 0.636
[0.466 ; 0.736] | 0.000
[0.000 ; 0.000] |
| Parameter
(unit) | N | Sample Range | r
(95% CI) | Slope
(95% CI) | Intercept
(95% CI) |
| LYM% (%) | 821 | 0.7 - 99.2 | 0.985
[0.983;0.987] | 0.990
[0.984 ; 0.996] | 0.685
[0.501 ; 0.875] |
| LYM# (109/L)
(103/µL) | 821 | 0.05 - 204.00 | 0.993
[0.993;0.994] | 1.005
[0.995 ; 1.015] | 0.064
[0.047 ; 0.080] |
| MON% (%) | 843 | 0.1 - 87.9 | 0.938
[0.93;0.946] | 1.008
[1.000 ; 1.042] | 0.402
[0.122 ; 0.600] |
| MON#
(109/L)
(103/µL) | 843 | 0.00 - 98.90 | 0.955
[0.949;0.961] | 1.128
[1.102 ; 1.152] | -0.028
[-0.041 ; -0.015] |
| NEU% (%) | 834 | 0.2 - 95.6 | 0.984
[0.982;0.986] | 0.988
[0.982 ; 0.995] | 0.373
[-0.051 ; 0.769] |
| NEU# (109/L)
(103/µL) | 834 | 0.0 - 75.3 | 0.968
[0.964;0.972] | 1.014
[1.008 ; 1.021] | 0.013
[-0.006 ; 0.031] |
| EOS% (%) | 928 | 0.0 - 78.1 | 0.984
[0.982;0.986] | 0.918
[0.902 ; 0.933] | 0.345
[0.310 ; 0.385] |
| EOS# (109/L)
(103/μL) | 928 | 0.00 - 23.30 | 0.976
[0.973;0.979] | 1.000
[0.984 ; 1.000] | 0.020
[0.020 ; 0.021] |
| BAS# (109/L)
(103/µL) | 897 | 0.00 - 12.30 | 0.902
[0.89;0.914] | 1.000
[0.818 ; 1.000] | -0.010
[-0.010 ; -0.006] |
| BAS% (%) | 897 | 0.0 - 13.1 | 0.712
[0.679;0.744] | 1.000
[0.931 ; 1.0] | -0.200
[-0.200 ; -0.1] |
| IMG% (%) | 834 | 0 - 37 | 0.867
[0.85;0.884] | 0.733
[0.674 ; 0.778] | 0.080
[0.050 ; 0.129] |
| IMG# (109/L)
(103/µL) | 834 | 0.00 - 72.40 | 0.982
[0.979;0.984] | 0.854
[0.802 ; 0.901] | 0.001
[-0.002 ; 0.002] |
| RET% (%) | 919 | 0.31 - 20.20 | 0.901
[0.888;0.913] | 1.020
[0.997 ; 1.045] | -0.140
[-0.182 ; -0.100] |
| RET# (109/L)
(103/µL) | 914 | 10 - 565 | 0.925
[0.916;0.934] | 0.997
[0.968 ; 1.026] | -3.355
[-5.626 ; -1.907] |
| CRC (%) | 919 | 0.1 - 12.7 | 0.939
[0.931;0.947] | 0.986
[0.961 ; 1.012] | -0.067
[-0.099 ; -0.034] |
| IRF | 914 | 0.00 - 0.54 | 0.778
[0.752;0.803] | 0.833
[0.807 ; 0.868] | 0.023
[0.017 ; 0.028] |
| RHCC (pg) | 913 | 12.7 - 49.1 | 0.654
[0.616;0.691] | 1.226
[1.159 ; 1.294] | -9.781
[-12.089 ; -7.528] |
| Parameter | N | Sample Range | r
(95% CI) | Slope
(95% CI) | Intercept
(95% CI) |
| BFWBC
(106/L) | 159 | 22 - 8940 | 0.923
[0.9;0.946] | 0.89
[0.86 ; 0.91] | 26.37
[18.62 ; 39.67] |
| BFRBC
(106/L) | 75 | 1500 - 3520000 | 0.999
[0.999;0.999] | 1.04
[1.0 ; 1.07] | -370.53
[-580.7 ; 61.48] |
| BFMN% (%) | 143 | 9.0 - 98.0 | 0.967
[0.957;0.978] | 0.90
[0.88 ; 0.91] | 9.75
[8.13 ; 11.05] |
| BFMN#
(106/L) | 143 | 10 - 3140 | 0.943
[0.925;0.961] | 1.09
[1.01 ; 1.25] | 23.05
[9.94 ; 35.66] |
| BFPN% (%) | 143 | 2.0 - 91.0 | 0.967
[0.957;0.978] | 0.90
[0.88 ; 0.92] | 0.64
[-0.29 ; 2.25] |
| BFPN#
(106/L) | 143 | 1 - 7430 | 0.911
[0.883;0.938] | 0.79
[0.77 ; 0.82] | 5.04
[1.68 ; 9.17] |

Table 22 - Whole Blood method comparison data summary

HORIBA ABX SAS, FRANCE

VOL 004-35

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Body Fluids

A method comparison study was conducted to assess the performance of the Yumizen H2500 device when compared to the predicate device. Sysmex XN-Series (XN-10. XN-20) (K112605). A total of 427 residual body fluid specimens from pediatric (≤21 years) and adult subjects including a wide variety of disease states (clinical conditions) were tested across three (3) clinical sites (two (2) US sites and one (1) European site).

The study was conducted using 174 synovial fluids, 138 serous fluids and 115 cerebrospinal fluids from a wide range of demographics (age and sex) and disease states (clinical conditions). Study sites aimed to cover the target assay reportable range for the parameters.

Each specimen was analysed as soon as possible from the time of collection in two (2) replicates on the Yumizen H2500 and one (1) replicate on the Sysmex XN-10 System, when sufficient volume was available. Specimens were tested on the Yumizen H2500 and the Sysmex XN-Series (XN-10, XN-20) within two (2) hours of each other.

A Passing-Bablok regression analysis was performed. Bias at medical decision points were also evaluated for all sites combined. All results were within the predefined acceptance criteria and found to be acceptable. Overall, the Yumizen H2500 demonstrated comparable performance to the predicate device, Sysmex XN-Series (XN-10, XN-20) (K112605) in an intended use population in a clinical laboratory setting.

A summary of the results is presented in the tables below:

Table 23 - Synovial Body Fluid method comparison data summary

40

Table 24 – Serous Body Fluid method comparison data Summary
Parameter	N	Sample Range	r
(95% CI)	Slope
(95% CI)	Intercept
(95% CI)
BFWBC
(106/L)	135	14 - 9370	0.965
[0.954;0.977]	0.91
[0.89 ; 0.94]	14.89
[6.58 ; 23.34]
BFRBC
(106/L)	87	1610 - 4590000	0.999
[0.999;1]	1.04
[1.02 ; 1.08]	31.75
[-231.53 ; 262.80]
BFMN% (%)	132	10.0 - 99.0	0.965
[0.954;0.977]	0.90
[0.85 ; 0.94]	11.66
[7.78 ; 15.94]
BFMN#
(106/L)	132	23 - 4590	0.954
[0.939;0.969]	1.00
[0.96 ; 1.04]	13.31
[7.09 ; 21.67]
BFPN% (%)	132	1.0 - 90.0	0.965
[0.954;0.977]	0.90
[0.85 ; 0.95]	-1.58
[-2.69 ; -0.67]
BFPN#
(106/L)	132	1 - 7560	0.972
[0.963;0.981]	0.78
[0.74 ; 0.82]	-1.36
[-2.82 ; 0.04]

Table 24 – Serous Body Fluid method comparison data summary

Table 25 – CSF Body Fluid method comparison data summary

| Parameter | N | Sample Range | r
(95% CI) | Slope
(95% CI) | Intercept
(95% CI) |
|------------------|-----|----------------|------------------------|-----------------------|-----------------------------|
| BFWBC
(106/L) | 109 | 5 - 8460 | 0.980
[0.973;0.988] | 0.99
[0.95 ; 1.02] | 5.14
[3.87 ; 7.25] |
| BFRBC
(106/L) | 71 | 1650 - 4690000 | 1.000
[1;1] | 1.07
[1.04 ; 1.08] | 15.80
[-533.69 : 487.19] |
| BFMN% (%) | 77 | 1 - 100 | 0.816
[0.738;0.887] | 0.94
[0.88 ; 1.04] | 10.87
[6.31 ; 14.89] |
| BFMN#
(106/L) | 77 | 6 - 2980 | 0.693
[0.566;0.8] | 1.11
[1.00 ; 1.18] | 6.36
[2.36 ; 11.25] |
| BFPN% (%) | 77 | 0 - 99 | 0.817
[0.739;0.888] | 0.94
[0.88 ; 1.05] | -5.36
[-13.33 ; -0.86] |
| BFPN#
(106/L) | 77 | 0 - 5940 | 0.863
[0.805;0.918] | 0.87
[0.81 ; 0.99] | -0.49
[-2.46 ; 0.58] |

41

b. Matrix Comparison:

Comparability between sampling types (capillary / venous)

The study was performed to demonstrate comparability between capillary whole blood samples and venous whole blood samples on the Yumizen H2500 device.

A total of 84 normal and pathological paired capillary and venous whole blood specimens were prospectively collected. Paired specimens collected from the same individuals were assayed in duplicate on the Yumizen H2500 device at one (1) clinical site. The clinical site aimed to enroll subject samples that covered all relevant medical decision points and were representative of the proposed analytical measurement ranges to the extent possible.

Bias was estimated at three points for each parameter: the low end of the distribution of observations, the mid-point, and the high end of the distribution, based on EP9-A3 guidelines. Acceptance criteria were met for all parameters at all levels. Therefore, the study results support the claim of using the two specimen types for measurement on the Yumizen H2500 device.

Comparability between body fluid anticoaqulants

The study was performed to demonstrate comparability between body fluid anticoagulants on the Yumizen H2500 device.

A total of 9 synovial body fluids without anticoagulant, 39 synovial body fluids with K2EDTA anticoagulant, 92 synovial body fluids with Lithium Heparin anticoagulant and 34 synovial body fluids with Sodium Heparin anticoagulant were run on the Yumizen H2500 device at three (3) clinical sites. In the Bland-Altman difference plots, a visual examination of each anticoagulant subgroup of samples was performed. No difference linked to anticoaqulant was observed on these graphs. No significant effect linked to the matrix was observed on these data.

A total of 82 serous body fluids without anticoagulant and 56 serous body fluids with K2EDTA were run on the Yumizen H2500 device at three (3) clinical sites.

In the Bland-Altman difference plots, a visual examination of each anticoagulant subgroup of samples was performed. No difference linked to anticoagulant was observed on these graphs. No significant effect linked to the matrix was observed on these data.

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Comparability between analytical modes

The study was performed to demonstrate equivalency between Yumizen H2500 available analytical modes:

Available Analytical Modes	Corresponding Analytical Cycle
DIF	DIF
DIR	DIR
RBC_PLTO	RBC_PLTO
DIF_LV	DIF_LV
CBC	DIF
RET	DIR
CBR	DIR

Table 26 - List of Yumizen H2500 Modes and cycles

There are seven (7) analytical modes based on four (4) different cycles only. The equivalency between those four (4) cycles: DIF, RBC PLTO and DIF LV was verified.

A total of 166 normal and pathological residual whole blood specimens were assayed in duplicate in the DIR and DIF modes on one (1) Yumizen H2500 at one (1) clinical site to compare performance between analytical modes, and the results were analyzed for all applicable parameters.

A total of 172 normal and pathological residual whole blood specimens were assayed in duplicate in the RBC_PLTO and DIF modes one (1) Yumizen H2500 at one (1) clinical site to compare performance between analytical modes, and the results were analyzed for all applicable parameters.

A total of 187 normal and pathological residual whole blood specimens were assayed in duplicate in the DIF_LV and DIF modes on one (1) Yumizen H2500 at one (1) clinical site to compare performance between analytical modes, and the results were analyzed for all applicable parameters.

Study site aimed to cover the target assay reportable range for the parameters.

Bias was estimated at three points for each parameter: the low end of the distribution of observations, the mid-point, and the high end of the distribution, based on EP9-A3 guidelines. Acceptance criteria were met for all parameters at all levels.

The results show comparable performance characteristics for all Yumizen H2500 modes.

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Comparability mode to mode

The study was performed to demonstrate comparability between automatic rack mode versus manual (STAT) mode with whole blood samples on the Yumizen H2500 device. A total of 83 normal and pathological residual whole blood samples were run in automatic rack mode version manual (STAT) mode on the Yumizen H2500 device at one (1) clinical site. The clinical site aimed to enroll subject samples that covered all relevant medical decision points and were representative of the proposed analytical measurement ranges to the extent possible.

Bias was estimated at three points for each parameter: the low end of the distribution of observations, the mid-point, and the high end of the distribution, based on EP9-A3 guidelines. Acceptance criteria were met for all parameters at all levels.

The results show comparable performance characteristics for all Yumizen H2500 modes.

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c. Clinical Sensitivity:

Flagging analysis was conducted to evaluate the flagging capabilities of the Yumizen H2500 using the flagging results obtained from the samples used in the method comparison study, from four (4) clinical sites, based on CLSI H20-A2 quidelines. A total of 456 residual normal (no flags, marked as negative) and abnormal (contained flags, marked as positive) whole blood samples were tested and compared to the reference (predicate or manual count results, depending on the parameter).

The results were classified according to the following categories:

TN (True negative): Yumizen H2500 result and reference result are both negative (normal sample).
Yumizen H2500 result and reference result are both positive TP (True positive): (abnormal sample).
FN (False Negative): Yumizen H2500 gives a neqative result (normal sample) whereas reference gives a positive result (abnormal sample).
FP (False Positive): Yumizen H2500 gives a positive result (abnormal sample) whereas reference gives a negative result (normal sample).

The estimated sensitivity, estimated specificity and estimated efficiency were calculated for each pathology and abnormality, using the following calculations:

Estimated sensitivity (%): TP / (TP+FN) x 100 Estimated specificity (%): TN / (TN+FP) x 100 Estimated efficiency (%): (TP+TN) / (TP+FN+FP+TN) x 100

The overall flagging capabilities of the Yumizen H2500 device met the predefined acceptance criteria for both sensitivity and specificity.

A summary of the results is presented in the table below:

| Category of
Abnormalities | N | TP | FP | EN | TN | Sensitivity
(95%CI) | Specificity
(95%CI) | Efficiency
(95%CI) |
|-------------------------------------------------------------------|-----|-----|----|----|-----|---------------------------|---------------------------|---------------------------|
| Any Morphological
Flag | 455 | 165 | 41 | 40 | 209 | 80.5%
(74.5% to 85.3%) | 83.6%
(78.5% to 87.7%) | 82.2%
(78.4% to 85.6%) |
| Any Distributional
Abnormality | 456 | 306 | 9 | 27 | 114 | 91.9%
(88.5% to 94.4%) | 92.7%
(86.7% to 96.1%) | 92.1%
(89.2% to 94.4%) |
| Any Morphological
Flag and/or
Distributional
Abnormality | 455 | 307 | 11 | 34 | 103 | 90.0%
(86.4% to 92.8%) | 90.4%
(83.5% to 94.5%) | 90.1%
(87.0% to 92.7%) |

Table 27 - Clinical Sensitivity Study acceptance criteria

45

C. Clinical Studies

Not applicable

D. Clinical Cut-Off

Not applicable.

46

E. Expected Values/Reference Range:

Whole Blood - Adult samples

The adult reference intervals study was conducted at two (2) US clinical sites to establish adult reference intervals for the Yumizen H2500 device. The study followed CLSI EP28-A3c quidelines and was performed using whole blood samples collected from 240 (120 male and 120 female) apparently healthy adults (>21 years). Each of the samples was analyzed on one Yumizen H2500 device for all parameters. The reference intervals were calculated for each parameter. The lower and upper limits of the 95% reference intervals were determined based on the 2.5th and 97.5th percentiles of all valid measurements for each sex group, respectively.

| Parameter | Table 28 - Whole blood - Adult reference intervals
Female | Male |
|-------------------------|--------------------------------------------------------------|------------|
| WBC (109/L) (103/μL) | 4.71-12.03 | 4.00-10.74 |
| RBC (1012/L) (106/μL) | 3.93-5.35 | 4.08-6.06 |
| HGB (g/dL) | 10.8-15.0 | 11.8-17.2 |
| HCT (%) | 33.8-46.2 | 35.9-50.6 |
| MCV (fL) | 77.8-95.8 | 69.5-96.5 |
| MCH (pg) | 25.2-32.0 | 22.3-32.2 |
| MCHC (g/L) | 313-344 | 313-347 |
| RDW-SD (fL) | 30.9-47.2 | 30.9-48.0 |
| RDW-CV (%) | 12.0-16.0 | 12.7-19.1 |
| PLT (109/L) (103/μL) | 183-402 | 144-379 |
| MPV (fL) | 8.0-11.2 | 7.3-11.6 |
| TNC (109/L) (103/μL) | 4.71-12.03 | 4.00-10.74 |
| NRBC# (109/L) (103/μL) | 0.00-0.00 | 0.00-0.00 |
| NRBC% (%) | 0.0-0.0 | 0.0-0.0 |
| LYM# (109/L) (103/μL) | 1.11-3.78 | 1.21-3.88 |
| LYM% (%) | 18.6-49.8 | 16.5-46.5 |
| MON# (109/L) (103/μL) | 0.27-0.97 | 0.28-1.04 |
| MON% (%) | 4.6-11.7 | 5.1-12.3 |
| NEU# (109/L) (103/μL) | 1.96-8.39 | 1.88-6.62 |
| NEU% (%) | 38.0-72.3 | 41.4-75.7 |
| EOS# (109/L) (103/μL) | 0.04-0.47 | 0.03-0.43 |
| EOS% (%) | 0.6-6.0 | 0.5-5.2 |
| BAS# (109/L) (103/μL) | 0.00-0.07 | 0.00-0.08 |
| BAS% (%) | 0.0-1.2 | 0.0-1.1 |
| IMG# (109/L) (103/μL) | 0.01-0.15 | 0.00-0.19 |
| IMG% (%) | 0.1-2.0 | 0.1-2.5 |
| PLT-Ox (109/L) (103/μL) | 175-420 | 134-370 |
| LPF (%) | 1.3-8.0 | 1.0-11.5 |
| RET# (109/L) (103/μL) | 26-118 | 27-137 |
| RET% (%) | 0.55-2.62 | 0.54-2.39 |
| CRC (%) | 0.50-2.35 | 0.53-2.49 |
| IRF | 0.00-0.16 | 0.01-0.20 |
| RHCC (pg) | 24.7-35.2 | 25.1-36.8 |

Table 28 - Whole blood – Adult reference intervals

47

Whole Blood - Pediatric samples

The pediatric reference intervals study was conducted at two (2) US clinical sites to establish pediatric reference intervals for the Yumizen H2500 device. The study followed CLSI EP28-A3c guidelines and was performed using pediatric venous or capillary whole blood samples collected from at least 80 (approx. 40 male and 40 female) apparently healthy neonates, infants, children and adolescents (

Intended Use / Indications for Use

Product codes (comma separated list FDA assigned to the subject device)

Device Description

Mentions image processing

Mentions AI, DNN, or ML

Input Imaging Modality

Anatomical Site

Indicated Patient Age Range

Intended User / Care Setting

Description of the training set, sample size, data source, and annotation protocol

Description of the test set, sample size, data source, and annotation protocol

§ 864.5220 Automated differential cell counter.

K232946 - Caroline Ferrer

Min Wu -

Indications for Use

CONTINUE ON A SEPARATE PAGE IF NEEDED.

DO NOT SEND YOUR COMPLETED FORM TO THE PRA STAFF EMAIL ADDRESS BELOW.

510(k) Safety and Effectiveness Summary

Submitted by:

l. Background Information

A. 510(k) number

K232946

B. Applicant

HORIBA ABX SAS (Brand HORIBA Medical)

C. Proprietary and Established Names

D. Regulatory Information

Submission / Device Overview ll.

A. Purpose for Submission

B. Parameters

C. Type of Test

���. Intended Use/Indications for Use

A. Intended Use(s)

B. Indications for Use

C. Special Conditions for Use Statement

IV. Device/System Characteristics

A. Device Description

B. Principles of Operation

Table 1 - Analvtical modes

C. Instrument Description

Yumizen H2500

b. Specimen Identification:

c. Specimen Sampling and Handling:

d. Calibration:

e. Quality Control:

V. Substantial Equivalence Information

A. Predicate Device Name(s)

B. Predicate 510(k) Number(s)

K112605

C. Comparison with Predicate

Table 2 - Comparison with predicate

VOL 004 : 510(k) Safety and Effectiveness Summary Yumizen H2500 Traditional 510(k): Supplement to Original Submission K232946

VI. Standards/Guidance Documents Referenced

Table 3 - List of standards

VOL 004 : 510(k) Safety and Effectiveness Summary Yumizen H2500 Traditional 510(k): Supplement to Original Submission K232946

Performance Characteristics (if/when applicable) VII.

Repeatability - Whole Blood

Table 5 - Repeatability – Whole Blood abnormal samples

Repeatability – Body Fluid

Table 6 - Repeatability – Body Fluid serous samples

Reproducibility - Whole Blood

Table 9 - Reproducibility ABX Difftrol - combined sites analysis

VOL 004 : 510(k) Safety and Effectiveness Summary Yumizen H2500 Traditional 510(k): Supplement to Original Submission K232946

Reproducibility - Body Fluids

VOL 004 : 510(k) Safety and Effectiveness Summary Yumizen H2500 Traditional 510(k): Supplement to Original Submission K232946

b. Linearity:

Linearity - Whole Blood

Linearity - Body Fluids

c. Analytical Specificity/Interference:

Interferences - Whole Blood

Hemoglobin, Lipemia, Bilirubin, Glucose and Yeast

Whole Blood Parameters Potential Interferents

Whole Blood Intrinsic Interferences

Table 15 - Potential interferent study summary

Interferences - Body Fluids

Hemoglobin, Lipemia, Bilirubin, Total Protein and Yeast

Table 16 - Whole Blood Parameters - Potential Interferents

Body Fluid Intrinsic Interferences

d. Traceability, Stability, Expected Values:

Stability - Whole Blood samples:

Sample stability study results Whole Blood -

��. Intended Use/Indications for Use