FDA 510(k) Search - By Innolitics (SaMD and AI Experts)

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 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.

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.

AI/ML Overview

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

Since specific acceptance criteria values were not explicitly stated for all performance aspects, I will infer them as generally "met predefined acceptance criteria" or "demonstrated comparable performance" where stated in the document.

Test Category	Parameter	Acceptance Criteria (Inferred)	Reported Device Performance
Analytical Performance
Repeatability (Whole Blood)	All parameters	All components of variation met predefined acceptance criteria.	Max %CV and Max SD values were reported for various parameters across normal, low, and high target ranges (Tables 4 and 5) and were found to meet the predefined acceptance criteria. For example, normal WBC has Max %CV of 2% and Max SD of 0.150, while high WBC (10-30 10^9/L) has Max %CV of 1.9% and Max SD of 0.330.
Repeatability (Body Fluid)	All parameters	All components of variation met predefined acceptance criteria.	Max %CV and Max SD values were reported for various parameters (BFWBC, BFRBC, BFPN#, BFPN%, BFMN#, BFMN%) across different levels and fluid types (serous, synovial, CSF) (Tables 6, 7, 8) and were found to meet the predefined acceptance criteria. For example, BFWBC (Level 1) for serous fluids has Max %CV of 10.4% and Max SD of 8.5.
Reproducibility (Whole Blood)	All parameters	Met acceptance criteria per CLSI EP05-A3.	Detailed SD and CV% reported for within-run, between-run, between-day, and between-site variations for whole blood control materials (ABX Difftrol - Table 9, ABX Minotrol Retic - implicit in text, though table only provided for Difftrol). All results met the acceptance criteria. For example, WBC (Low) total CV% was 3.62%; HGB (Normal) total CV% was 0.89%.
Reproducibility (Body Fluids)	All parameters	Met acceptance criteria per CLSI EP05-A3.	Detailed SD and CV% reported for within-run, between-run, between-day, and between-site variations for body fluid control material (BFTROL - Table 11). All results met the acceptance criteria. For example, BFWBC (Level 2) total CV% was 6.34%; BFRBC (Level 3) total CV% was 3.55%.
Linearity (Whole Blood)	WBC, TNC, RBC, HGB, HCT, PLT, PLT-Ox, RET#, NRBC#	All results met predefined acceptance criteria and were acceptable.	Linearity ranges were established for each parameter (Table 12). For example, WBC: 0.06 – 344.50 10^9/L; HGB: 0.5 – 25.8 g/dL.
Linearity (Body Fluids)	BFWBC, BFRBC	All results met predefined acceptance criteria and were acceptable.	Linearity ranges were established for BFWBC (3 – 11 345 10^6/L) and BFRBC (1079 – 5 394 633 10^6/L) (Table 13).
Interferences (Whole Blood)	All parameters	No interference detected or no significant effect. Conjugated bilirubin may have a significant effect on low HGB levels.	The device was found not susceptible to interference from Hemoglobin, Lipemia, Bilirubin (except conjugated bilirubin on low HGB), Glucose, and Yeast for various parameters. Intrinsic interferences from elevated WBC, RBC, and PLT measurands showed no interference for specific parameters. Some potential impacts (e.g., PLT-Ox and LYM# from macrothrombocytosis; RDW-SD from dual RBC population) were noted, but overall deemed acceptable within context of the study (Table 15).
Interferences (Body Fluids)	All parameters	No interference detected or no significant effect. Interference from yeast was detected.	No significant effect was detected on BFWBC, BFRBC from Hemoglobin, Lipemia, Bilirubin, and Total Protein across various fluid types. Interference from yeast was detected. Known interferences from crystals and liposomal particles were acknowledged as per literature (Table 17).
Stability (Whole Blood)	All parameters	Acceptance criteria for each parameter met for defined time intervals.	Whole blood samples are stable for 24h at room temperature for CBC/LMNE/NRBC/RET parameters, and 48h (CBC/LMNE/NRBC) or 72h (RET) at refrigerated temperature (Table 18).
Stability (Body Fluid)	All parameters	Acceptance criteria for sample stability (max bias) met.	Serous and synovial fluids are stable for 24h at room temperature for BFWBC/BFRBC/BFPN/BFMN parameters. CSF is stable for 4h at room temperature for BFWBC/BFRBC/BFPN/BFMN parameters (Table 19).
Detection Limits (Whole Blood)	WBC, TNC, RBC, HGB, HCT, PLT, PLT-Ox, RET#	All results met predefined acceptance criteria and were acceptable.	LoB, LoD, and LoQ values were determined for various parameters (Table 20). For example, WBC: LoB 0.05, LoD 0.07, LoQ 0.10 (10^9/L).
Detection Limits (Body Fluid)	BFWBC, BFRBC	All results met predefined acceptance criteria and were acceptable.	LoB, LoD, and LoQ values were determined for BFWBC (LoB 2, LoD 4, LoQ 5 (10^6/L)) and BFRBC (LoB 500, LoD 1000, LoQ 1500 (10^6/L)) (Table 21).
Carry-over (Whole Blood)	All parameters	All carry-over results are within specifications.	Not applicable - Carry-over results are within specifications.
Carry-over (Body Fluids)	All parameters	All carry-over results are within specifications.	Not applicable - Carry-over results are within specifications.
Comparison Studies
Method Comparison (Whole Blood)	All parameters	All results were within the predefined acceptance criteria and acceptable. Yumizen H2500 demonstrated comparable performance to predicate device.	Passing-Bablok regression analysis (r, slope, intercept with 95% CI) was performed (Table 22). Correlations ranged from 0.184 (MCHC, potentially an outlier or specific context needed) to 0.998 (HGB). Most parameters showed high correlations and slopes close to 1, with intercepts close to 0, indicating strong agreement with the predicate device. For example, WBC: r=0.996, slope=1.012, intercept=0.045.
Method Comparison (Body Fluids)	All parameters	All results were within the predefined acceptance criteria and acceptable. Yumizen H2500 demonstrated comparable performance to predicate device.	Passing-Bablok regression analysis (r, slope, intercept with 95% CI) was performed for synovial, serous, and CSF (Tables 23, 24, 25). Correlations varied, with BFRBC showing very high correlation (0.999-1.000) across all fluid types. Other parameters showed good correlations (e.g., BFWBC r=0.923-0.980, BFMN% r=0.816-0.967) indicating comparable performance. For example, CSF BFWBC: r=0.980, slope=0.99, intercept=5.14.
Comparability (Sampling types)	All parameters	Acceptance criteria met for all parameters at all levels.	Bias estimated at low, mid, and high points for each parameter showed comparability between capillary and venous whole blood samples.
Comparability (Anticoagulants)	All parameters	No difference linked to anticoagulant or significant effect linked to matrix observed.	Visual examination of Bland-Altman difference plots showed no difference linked to K2EDTA, Lithium Heparin, or Sodium Heparin anticoagulants for synovial fluid. No difference linked to anticoagulant for K2EDTA in serous fluids.
Comparability (Analytical Modes)	All parameters	Acceptance criteria met for all parameters at all levels.	Bias estimated at low, mid, and high points for each parameter demonstrated comparable performance characteristics for all Yumizen H2500 modes (DIF, DIR, RBC_PLTO, DIF_LV).
Comparability (Manual vs Auto)	All parameters	Acceptance criteria met for all parameters at all levels.	Bias estimated at low, mid, and high points for each parameter demonstrated comparable performance characteristics between automatic rack mode and manual (STAT) mode.
Clinical Sensitivity	Morphological Flags, Distributional Abnormality, Combined Flags	Met predefined acceptance criteria for both sensitivity and specificity.	Sensitivity: 80.5% (Morphological), 91.9% (Distributional), 90.0% (Combined). Specificity: 83.6% (Morphological), 92.7% (Distributional), 90.4% (Combined). Efficiency: 82.2% (Morphological), 92.1% (Distributional), 90.1% (Combined) (Table 27).
Expected Values/Reference Range	All parameters	Establishment of reference intervals.	Reference intervals were established for adult (male/female) and pediatric (neonate, infant, child, adolescent) whole blood samples, and for synovial, serous, and CSF body fluids (Tables 28, 29, 30). This demonstrates the ability to define expected values for various populations.

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

Repeatability:
- Whole Blood: 116 residual K2EDTA whole blood samples (mixed normal and contrived for extremes) used for within-run repeatability.
- Body Fluid: 87 residual body fluid samples (Synovial, Serous and Cerebrospinal Fluids) (mixed normal and contrived for extremes) used for within-run repeatability.
- Provenance: Retrospective, samples around medical decision levels or contrived to cover analytical measuring range. Collected from multiple sites (4 test sites for whole blood, 4 test sites for body fluid). Country of origin is not explicitly stated beyond "4 test sites" which include "2 US sites and 2 European sites" for some studies, implying data from both regions.
Reproducibility:
- Whole Blood: Three levels of control material (ABX Difftrol and ABX Minotrol Retic) run in duplicate twice a day for a minimum of 20 days (total 320 runs per level for each parameter if 4 sites and 2 runs/day * 20 days * 2 replicates * 2 instruments = 320 runs).
- Body Fluids: Two levels of control material (BFTROL) run in duplicate twice a day for a minimum of 20 days (total 320 runs per level for each parameter).
- Provenance: Control materials, conducted at 4 test sites (4 instruments, one per site).
Linearity:
- Whole Blood: Minimum of seven concentration levels (commercial or prepared from dilutions) for each parameter. Each level tested in a minimum of 4 replicates on 2 instruments using 2 reagent lots.
- Body Fluids: Mimimum of seven concentration levels (prepared from dilutions) for each parameter. Each level tested in a minimum of 4 replicates on 2 instruments using 2 reagent lots.
- Provenance: One test site (for both whole blood and body fluids).
Interferences:
- Whole Blood: Two concentration levels of interferent (Hemoglobin, Lipemia, Bilirubin, Glucose, Yeast) for direct interference. A subset of samples from the method comparison study (unique, native whole blood specimens identified with potential interference analysis, minimum of 17 specimens per interferent) for intrinsic interferences.
- Body Fluids: Two concentration levels of interferent (Hemoglobin, Lipemia, Bilirubin, Total Protein, Yeast) for direct interference. A subset of samples from the method comparison study (unique, native body fluid specimens identified with potential interferents) for intrinsic interferences.
- Provenance: 4 test sites (for both whole blood and body fluids).
Stability:
- Whole Blood: 14 whole venous blood specimens.
- Body Fluid: 28 body fluid specimens (13 serous, 7 synovial, and 8 cerebrospinal fluids).
- Provenance: 3 test sites for whole blood, 2 test sites for body fluid.
Detection Limits (LoB, LoD, LoQ):
- Six blank samples, six low concentration samples (for LoD), at least four low concentration samples (for LoQ). Each sample run 10 repeated times.
- Provenance: Not specified beyond "different analyzers" and "two different reagent lots".
Carry-over:
- High and low target value samples run consecutively (3 high, 3 low) for each parameter. Three sets of carry-over sequences.
- Provenance: One test site, three analyzers.
Method Comparison:
- Whole Blood: 969 venous and/or capillary specimens (pediatric (≤21 years) and adult). 143 with known medical conditions. Maximum 10% contrived.
- Body Fluids: 427 residual body fluid specimens (pediatric (≤21 years) and adult) - 174 synovial, 138 serous, 115 CSF.
- Provenance: 4 clinical sites (2 US sites and 2 European sites for whole blood); 3 clinical sites (2 US sites and 1 European site for body fluids). Mostly retrospective (leftover specimens).
Matrix Comparison (Comparability between sampling types):
- 84 normal and pathological paired capillary and venous whole blood specimens.
- Provenance: One clinical site. Prospective collection.
Matrix Comparison (Comparability between body fluid anticoagulants):
- Synovial fluid: 9 without anticoagulant, 39 with K2EDTA, 92 with Lithium Heparin, 34 with Sodium Heparin.
- Serous fluid: 82 without anticoagulant, 56 with K2EDTA.
- Provenance: 3 clinical sites.
Matrix Comparison (Comparability between analytical modes):
- DIR vs DIF: 166 normal and pathological residual whole blood specimens.
- RBC_PLTO vs DIF: 172 normal and pathological residual whole blood specimens.
- DIF_LV vs DIF: 187 normal and pathological residual whole blood specimens.
- Provenance: One clinical site for each comparison.
Matrix Comparison (Comparability mode to mode):
- 83 normal and pathological residual whole blood samples. (Automatic rack mode vs manual STAT mode).
- Provenance: One clinical site.
Clinical Sensitivity:
- 456 residual normal and abnormal whole blood samples (from method comparison study).
- Provenance: 4 clinical sites.
Expected Values/Reference Range:
- Adult Whole Blood: 240 apparently healthy adults (120 male, 120 female).
- Pediatric Whole Blood: At least 80 apparently healthy neonates, infants, children, and adolescents (

Summary

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.”