The PENTRA XLR is a quantitative multi-parameter automated hematology analyzer for in vitro diagnostic use in clinical laboratories to identify and enumerate the following parameters: WBC, RBC, HCT, MCV, MCH, MCHC, RDW, PLT, MPV, LYM (#, %), MON (#, %), NEU (#, %), EOS (#, %), BAS (#, %), as well as the Reticulocyte parameters RET (#, %), CRC, and IRF in K2EDTA and K3EDTA anticoagulated venous whole blood samples from patients ≥ 18 years of age.

Device Description

The PENTRA XLR is a device modification to the ABX PENTRA 80 (K024002), which consists in the addition of the measurement of Reticulocytes (RET) parameters to the existing Complete Blood Count (CBC) and Differential (DIFF) counts already performed by the analyzer. The additional RET mode, based on the use of Thiazol orange reagent and fluorescence detection by optical bench, is independent from the modes already existing on the ABX PENTRA 80: the CBC and the CBC+DIFF modes, as there have been no modifications to the existing mechanical and analytical portions of the original device.

AI/ML Overview

Here's an analysis of the acceptance criteria and study details for the HORIBA ABX SAS PENTRA XLR device, based on the provided text:

Important Note: The provided text is a 510(k) Summary, which typically focuses on demonstrating substantial equivalence to a predicate device rather than presenting a full, independent validation study in the format one might expect for a research paper. Therefore, some details like specific expert qualifications or adjudication methods for ground truth might not be explicitly stated for all aspects if they were part of the predicate device's original validation or are assumed by industry standards for this type of device.

1. Table of Acceptance Criteria and Reported Device Performance (Reticulocyte Parameters)

The document focuses on the newly added Reticulocyte (RET) parameters for the PENTRA XLR. Performance for existing CBC and DIFF parameters is stated to be unchanged from the predicate device (ABX PENTRA 80, K024002).

Performance Metric	Parameter	Acceptance Criteria (PENTRA XLR Specified)	Reported Device Performance (PENTRA XLR)
Analytical Sensitivity (LoQ)	RET%	N/A (Lowest value with r² > 0.98 in linearity)	0.7%
	RET#	N/A (Lowest value with r² > 0.98 in linearity)	0.01 x 10⁶/mm³
Precision (Repeatability) - CV%	RET% (Normal Level)	< 12	Met specifications
	RET% (High Level)	< 8	Met specifications
	RET# (Normal Level)	< 20	Met specifications
	RET# (High Level)	< 10	Met specifications
	CRC (Normal Level)	< 15	Met specifications
	CRC (High Level)	< 10	Met specifications
	IRF (Low Level)	SD < 0.04	Met specifications
	IRF (Normal Level)	< 25	Met specifications
	IRF (High Level)	< 15	Met specifications
Precision (Reproducibility) - CV% Total	RET% (Low Level Control)	18%	Met specifications
	RET% (Normal Level Control)	10%	Met specifications
	RET% (High Level Control)	8%	Met specifications
	RET# (Low Level Control)	18%	Met specifications
	RET# (Normal Level Control)	10%	Met specifications
	RET# (High Level Control)	8%	Met specifications
	CRC (Low Level Control)	18%	Met specifications
	CRC (Normal Level Control)	10%	Met specifications
	CRC (High Level Control)	8%	Met specifications
	IRF (Low Level Control)	15%	Met specifications
	IRF (Normal Level Control)	12%	Met specifications
	IRF (High Level Control)	10%	Met specifications
Linearity / AMR	RET%	N/A (Linearity across claimed range with polynomial regression)	0.7 - 27%
	RET#	N/A (Linearity across claimed range with polynomial regression)	0.01 - 0.5 (x10⁶/mm³)
Carryover	RET%	< 1%	Within specifications
	RET#	< 1%	Within specifications
Interference	Bias vs. Acceptable Limit	Remained below acceptable limit	No significant interference observed (Urea, bilirubin, lipemia, hemolysis)
	Comparable Effect	Observed similar effects to reference device	Abnormal RBC, Basophilic stippling, Cold agglutinins, Giant platelets, Hemolysis, Howell-Jolly Bodies, Leukocyte fragments, Nucleated erythrocytes, Pappenheimer bodies, Paraproteins, Platelet clumps, Platelet/erythrocyte coincidence
Sample Stability	RET%, RET#, CRC, IRF (Refrigerated)	48 hours	48 hours
	RET%, RET#, CRC, IRF (Room Temp)	24 hours	24 hours
Predicate Comparability	Bias at Low, Mid, High points	Acceptance criteria met	Met for all measurands at all levels (r²>0.95 for RET% and RET# stated in comparison table)
Anticoagulant Comparability	Bias at Low, Mid, High points	Acceptance criteria met	Met for all measurands at all levels (K2EDTA vs K3EDTA)
RBC Mode Comparability	Bias at Low, Mid, High points	Acceptance criteria met	Met for RBC in RET vs CBC modes
Reference Interval	(Specific ranges for male/female)	Defined reference interval for 95% of values, 90% CI for limits	Established with 122 female and 120 male samples

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

Precision (Repeatability): Minimum of 10 normal and 5 abnormal fresh whole blood samples collected into K2EDTA. Data Provenance: Fresh whole blood samples, collected at 3 different clinical sites (implicitly prospective).
Precision (Reproducibility): One single lot of control material (Minotrol Retic).
Linearity / AMR: Commercial Linearity kits.
Carryover: Alternating high and low concentration samples.
Interfering Substances:
- Addition Method: Samples with potential interfering substances added vs. control portions.
- Comparison Method: 10 to 20 patient specimens per group with known or potential reticulocyte interferents, and control samples.
Sample Stability: 10 whole venous blood specimens collected in K2EDTA. Data Provenance: US, implicitly prospective.
Comparability with Predicate Device: Total of 376 whole blood specimens collected in K2EDTA from adult patients. Data Provenance: US, from three test sites, collected prospectively or not (retrospective/prospective mix).
Comparability between Anticoagulant types: Total of 90 normal and pathological blood specimens. Data Provenance: US, from two sites, specifically prospectively collected for this study.
Comparability between CBC and RET modes for RBC: Total of 107 normal and pathological blood specimens collected in K2EDTA. Data Provenance: France, from one site.
Reference Interval: 242 normal adult samples (122 female and 120 male) collected in K2EDTA. Data Provenance: US, from two test sites.

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

The document does not explicitly mention the use of experts to establish ground truth in the traditional sense (e.g., for image interpretation or diagnosis). For an automated hematology analyzer measuring quantitative parameters, the "ground truth" for method comparison and accuracy studies is typically a reference measurement procedure, sometimes a manual count (e.g., manual reticulocyte count) or a highly accurate predicate device or method.

In this case:

Comparability with Predicate Device: The ABX PENTRA DX 120 (K991839) served as the reference method for evaluating the new RET parameters. This is an existing FDA-cleared automated hematology analyzer.
Interfering Substances (Comparison Method): ABX PENTRA DX 120 (K991839) was also used as the comparative measurement procedure.

Since the device evaluates quantitative hematological parameters, human expert visual review (e.g., microscopic differentiation) or adjudication is typically not the primary "ground truth" for the measured values themselves, which are generated parametrically. Ground truth for diagnosis based on these values might involve experts, but that's beyond the scope of device performance.

4. Adjudication Method for the Test Set

No explicit adjudication method (like 2+1 or 3+1 consensus) is described or would typically be applicable for the direct measurement of quantitative hematology parameters by an automated analyzer, as outlined above. The evaluation relies on statistical comparison against a reference method or against established internal specifications.

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

No MRMC comparative effectiveness study was done. This type of study is more common for diagnostic devices where human readers interpret outputs (e.g., radiographs, pathology slides). The PENTRA XLR is an automated analyzer producing quantitative values, not interpretations requiring human reading.

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

Yes, the studies described are essentially standalone performance studies for the algorithm (the automated analyzer). There is no "human-in-the-loop" component described for the measurement of the parameters. The output is a direct quantitative reading from the instrument.

7. Type of Ground Truth Used

The ground truth used depends on the specific study:

Analytical Sensitivity, Precision, Linearity, Carryover: Internal specifications, commercial linearity kits with "expected values" considered "true values," and statistical analysis against these benchmarks.
Interfering Substances: Comparison against a predicate device (ABX PENTRA DX 120) and acceptable bias limits.
Sample Stability: Comparison against an initial measurement (T0) of the same sample.
Comparability with Predicate Device: Measurements from the legally marketed predicate device, ABX PENTRA DX 120 (K991839).
Comparability between Anticoagulant types & RBC Mode Comparability: Statistical comparison between measurements obtained from different conditions on the PENTRA XLR itself.
Reference Interval: Statistical analysis of normal adult samples according to CLSI EP28-A3 guidelines.

8. The Sample Size for the Training Set

The document does not provide a specific sample size for a "training set." This is an automated diagnostic device, not a machine learning model in the contemporary sense that would undergo explicit "training" with a labeled dataset in the way a deep learning algorithm might. The device's "training" and calibration would be part of its engineering development, using internal standards and optimization, rather than a publicly reported "training set." The focus of this 510(k) is on the validation and verification of its analytical performance.

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

As noted above, a distinct "training set" with established ground truth as understood in machine learning contexts is not directly applicable or described here. The instrument's operational principles are based on established impedance and fluorescence cytochemistry, not a learned model from a large, expert-labeled dataset for classification/detection. Therefore, the concept of "ground truth for the training set" isn't explicitly addressed in this type of submission for this kind of device.

Summary

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

December 9, 2015

HORIBA ABX SAS HORIBA MEDICAL Ms. Caroline Ferrer Regulatory Affairs Manager Parc Euromédecine Rue du Caducée - BP7290 34184 Montpellier Cedex 4, France

Re: K151133

Trade/Device Name: PENTRA XLR Regulation Number: 21 CFR 864.5220 Regulation Name: Automated differential cell counter Regulatory Class: Class II Product Code: GKZ Dated: November 6, 2015 Received: November 9, 2015

Dear Ms. 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 (Act) that do not require approval of a premarket approval application (PMA). You may, therefore, market the device, subject to the general controls provisions of the Act. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.

If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. In addition, FDA may publish further announcements concerning your device in the Federal Register.

Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must

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comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Part 801); medical device reporting (reporting of medical device-related adverse events) (21 CFR 803); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

If you desire specific advice for your device on our labeling regulation (21 CFR Part 801), please contact the Division of Industry and Consumer Education at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address

http://www.fda.gov/MedicalDevices/Resourcesfor You/Industry/default.htm. Also, please note the regulation entitled. "Misbranding by reference to premarket notification" (21CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to

http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm for the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance.

You may obtain other general information on your responsibilities under the Act from the Division of Industry and Consumer Education at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address

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

Sincerely vours.

Leonthena R. Carrington -S

Leonthena R. Carrington, MS, MBA, MT(ASCP) Director Division of Immunology and Hematology Devices Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health

Enclosure

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DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration

Indications for Use

510(k) Number (if known) K151133

Device Name PENTRA XLR

Indications for Use (Describe)

Type of Use (Select one or both, as applicable)
	Prescription Use (Part 21 CFR 801 Subpart D) Over-The-Counter Use (21 CFR 801 Subpart C)

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Premarket Notification [510(k)] Summarv

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

The assigned 510(k) number: K151133

1.0 Sumitted bv : Company: HORIBA ABX SAS HORIBA MEDICAL Parc Euromédecine Rue du Caducée - BP 7290 34184 Montpellier cedex 4 FRANCE

Contact Person: Caroline Ferrer (caroline.ferrer@horiba.com) Telephone: + (33) 4 67 14 1843 Fax: + (33) 4 67 14 1517

2.0 Date Submitted :

November 2, 2015

3.0 Device Name and Classification : Trade/Proprietary Name: PENTRA XLR

Classification:

Device:	Counter, differential cell
Panel:	81 Hematology
Regulation number:	864.5220
Product Code:	GKZ
Class:	II

4.0 System description : 4.1 Device Description

The additional RET mode, based on the use of Thiazol orange reagent and fluorescence detection by optical bench, is independent from the modes already existing on the ABX PENTRA 80: the

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CBC and the CBC+DIFF modes, as there have been no modifications to the existing mechanical and analytical portions of the original device.

The existing fundamental scientific technology for the analyzer itself has not changed. Including, hematological parameters for complete blood count and differential leucocyte count, the reagents and controls, measuring principles, and the principles of operation are the same as previously cleared by the FDA. Refer to Table I.

The parameters already available on the ABX PENTRA 80 are unchanged:

CBC parameters: WBC, RBC, HGB, HCT, MCV, MCH, MCHC, RDW, PLT, MPV -
DIFF parameters: LYM#, LYM%, MON%, NEU#, NEU%, EOS#, EOS%, -BAS#, BAS%

The additional Reticulocytes parameters are the following: RET#: Reticulocvte Absolute Value RET%: Reticulocyte Percentage CRC: Corrected Reticulocyte Count IRF: Immature Reticulocyte Fraction

RBC parameter is as well reported in RET mode.

Software changes reflect routine updates to the cycle operation, increased user interface options, and the support of the Reticulocyte counting.

4.2 Principles of Operation

The PENTRA XLR performs hematology analyses using the following methods:

RBC / PLT: Impedance
WBC: Impedance ●
HGB: Spectrophotometry
DIFF: Impedance with hydrofocus Cytometry and Cytochemistry (DHSS)
. MCV: Calculated
. RET: Fluorescence and Impedance

The Principles of Operation for the parameters already existing on the ABX Pentra 80 are unchanged, and are therefore not explained again.

The Principle of Operation for the Reticulocyte Parameters is described below.

The instrument samples 35 uL of blood and injects 10 uL of it in the DIL1 chamber. It then mixes it with 1.7 mL of ABX Diluent. Then the instrument samples 28 uL of diluted blood and mixes it with 2.5 mL of ABX Fluocyte.

This reagent contains a fluorescent stain which is specific to nucleic acids: thiazol orange (Thiazol orange is a patented product from Becton Dickinson, San Jose, CA, USA).

The dilution is warmed at 35°C for 50 seconds. The stain molecules enter through the cell membrane and fix the ribonucleic acid molecules. This binding gives an increase of the

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fluorescence (enhancement: ~3000x). After 50 seconds, the solution is transferred to the laser optical bench to be measured.

The laser optical bench simultaneously measures the fluorescence of the cells passing through the measuring point into the flowcell, and the volume by impedance. A cell passing through the flowcell gives two types of information:

The size of the cell measured by resistivity (Cell Impedance Signal),
The fluorescence signal (Orthogonal Fluorescence Light OFL).

OFL: The fluorescence is collected using:

a lens focused on the optical flowcell and located at 90° from the laser beam,

an interferential filter specific to the thiazol orange stain selecting only the fluorescent wavelength,
an avalanche photodiode.

Reticulocvte Matrix:

The Reticulocytes matrix is generated from two measurements: resistivity volume (CIS) and orthogonal fluorescence (OFL) of cells according to the X and Y axes respectively.

Mature red blood cells without RNA show little or no fluorescent signal. They are located at the bottom of the matrix, and horizontally distributed according to their MCV and RDW. Reticulocytes are separated from the red blood cells by their fluorescence which is proportional to the RNA content and their immaturity.

The most fluorescent elements, which are saturated at the top of the matrix, are the most immature. Erythroblasts may also be found in this area.

4.3 Modes of Operation

Measurement modes:

The PENTRA XLR instrument can operate in:

CBC mode (Complete Blood Count)
DIFF mode (CBC + WBC Differential)
RET mode (Reticulocytes + RBC)

Sampling modes:

The PENTRA XLR operates in:

Automatic sampling (auto mixer and auto loader) for CBC and DIFF modes only ● or
. Manual sampling (STAT mode) for CBC, DIFF and RET modes.

Therefore, for the RET mode, only the manual sampling (STAT mode) is available.

4.4 Specimen Identification

Tube sample ID can be identified manually or by double barcode label reading.

4.5 Calibration

Calibration is a procedure that is performed during specific situations such as installation, maintenance or service intervention. It is performed by a HORIBA ABX SAS representative. It

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ensures that the precision and accuracy of the analyzer are acceptable, so that accurate measurements are performed by the analyzer.

The RET measurement is adjusted by HORIBA Medical technician upon the PENTRA XLR installation and according to procedure described in the User Manual.

4.6 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.

The RET parameters are controlled with a specific Quality Control; ABX MINOTROL RETIC, already cleared by 510(k) K94336 as Retic CONTROL-H Hematology Control, R&D Systems, Inc.

4.7 Software

HORIBA ABX SAS's Hazard Analysis and Software Development process for this product are included in this submission.

5.0 Intended use

5.1 Indications for Use :

The PENTRA XLR is a quantitative multi-parameter, automated hematology analyzer for in vitro diagnostic use in clinical laboratories to identify and enumerate the following parameters: WBC, RBC, HGB, HCT, MCV, MCH, MCHC, RDW, PLT, MPV, LYM (#, %), MON (#, %), NEU (#, %), EOS (#, %), BAS (#, %), as well as the Reticulocyte parameters RET (#, %), CRC, and IRF in K2EDTA and K3EDTA anticoagulated venous whole blood samples from patients ≥ 18 years of age.

5.2 Special Conditions for Use Statements:

For prescription use only.

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6.0 Comparison with the original device : Similarities

Item	PENTRA 80 (K024002) Original Device	PENTRA XLR Modified device
Manufacturer	HORIBA ABX SAS	Same
Type of product	Automated blood cell counter	Same
Parameters	Complete Blood Cell Count (CBC)WBC, RBC, HGB, HCT, MCV, MCH,MCHC, RDW, PLT, MPV	Same

	Leukocyte Differential (DIFF):NEU (# and %), LYM (# and %), MON(# and %), EOS (# and %), BAS (# and%)	Same
Sample types	K2 and K3EDTA anti-coagulated wholeblood	Same
Specimen volume	CBC mode: 35 μLCBC + DIFF mode: 53 µL	Same
Principlesofmeasurements	RBC / PLT: ImpedanceWBC: ImpedanceHGB: SpectrophotometryDIFF: Impedance with hydrofocusCytometry and Cytochemistry (DHSS)MCV: Calculated	Same
Reagents	ABX Diluent (10L, 20L)ABX CleanerABX Basolyse IIABX Eosinofix	Same
Calibrators	ABX Minocal	Same
Controls	ABX Minotrol 16ABX Difftrol	Same
Throughput	80 samples / hour	Same
Dimensions(Height x Width xDepth)	82cm x 57cm x 54cm	Same
Performancesforparameters in CBCand DIFF modes	PrecisionLinearityAccuracyLeukocyte DifferentiationSample stability	Same
Item	PENTRA 80 (K024002) Original Device	PENTRA XLR Modified device
Intended Use	The ABX PENTRA 80 Hematology Analyzer is a fully automated (microprocessor controlled) hematology analyzer used for the in vitro diagnostic testing of whole blood specimens.The ABX PENTRA 80 is able to operate either in complete blood count (CBC) mode or in CBC + 5 differential leucocyte count (5DIFF) mode.	The PENTRA XLR is a quantitative multi-parameter, automated hematology analyzer for in vitro diagnostic use in clinical laboratories to identify and enumerate the following parameters: WBC, RBC, HGB, HCT, MCV, MCH, MCHC, RDW, PLT, MPV, LYM#, LYM%, MON#, MON%, NEU#, NEU%, EOS#, EOS%, BAS#, BAS%, as well as the Reticulocyte parameters RET#, RET%, CRC, and IRF in K2EDTA and K3EDTA anticoagulated venous whole blood samples from patients ≥ 18 years of age.
RET mode	Not available	Additional Reticulocyte Count (RET):RET (in #, %), IRF (in %), CRC (in %)+ RBC (same as in CBC mode)
Specimen volume in RET mode	No RET Mode	Additional RET mode: 35 μL
RET Principles of measurements	No RET Mode	RET: Fluorescence and impedance
Hardware	Mechanical and pneumatic	Identical with addition of the following for RET measurement : diode laser, lens focused on the optical flowcell, an interferential filter specific to the thiazol orange stain selecting only the fluorescent wavelength, an avalanche photodiode.
Software	Windows-based software application	Identical. The software has been updated to integrate the RET measurement.
Reagents	ABX Lyse (ABX Alphalyse or ABX Lysebio)	ABX Lyse (ABX Lysebio only) ABX Fluocyte (specific reagent for Reticulocyte count, based on
		Thiazole Orange dye)
Controls	No Reticulocyte Control	ABX Minotrol Retic (specificcontrol for RET count)
Weight	55 kg	57 kg
Performances
Reticulocyteparameter	No Reticulocyte claim	Performance available for RET(in #, %), IRF (in %), CRC (in %)

The CBC and DIFF mode performance verification has been done and is on file at HORIBA ABX SAS. The performance of the PENTRA XLR RBC parameter obtained in RET mode has been verified during the RET parameters validation. The RBC parameter performance is identical to the performance obtained in CBC mode and previously detailed to FDA through K024002.

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Differences

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SECTION 007 : 510(k) Summary

7.0 Substantial Equivalence Information :

The following tables show the similarities and differences between the candidate device and its predicate device identified below.

7.1 Predicate Device Name and 510(k) number:

For the validation of the Reticulocyte parameters on the PENTRA XLR the following predicate device was used during the clinical evaluation:

Candidate device	Predicate device	Manufacturer	Predicate 510(k) numbers
PENTRA XLR	ABX PENTRA DX 120	HORIBA ABX SAS	K050719 K991839 K990311

7.2 Comparison with predicate Device : Similarities

Item	ABX PENTRA DX 120 (K991839) Predicate Device for RET parameters	PENTRA XLR Modified device
Manufacturer	HORIBA ABX SAS	Same
Type of product	Automated blood cell counter	Same
Diagnostic Parameters	RET: RET (#, %), IRF (%), MRV (Fl), CRC (%), RET L (%), RET M (%), RET H (%)	RET: RET (#, %), IRF (%), CRC (%)
Sample types	K2 and K3EDTA anti-coagulated whole blood	Same
RET Principles	Fluorescence and Impedance	Same
RET Reagents	ABX Fluocyte	Same
RET Methodology	ABX Fluocyte contains a fluorescent stain which is specific to nucleic acids: thiazol orange (Thiazol orange is a patented product from Becton Dickinson San	Same

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SECTION 007 : 510(k) Summary

Item	ABX PENTRA DX 120 (K991839)Predicate Device for RETparameters	PENTRA XLRModified device
	Jose, CA, USA).The stain molecules enter throughthe cell membrane and fix theribonucleic acid molecules. Thebinding gives an increase offluorescence. The laser opticalbench simultaneously measures thefluorescence of the cells passingthrough the measuring point into theflowcell, and volume byabsorbance. The size of the cell ismeasured by resistivity, thescattered light (FSL) is measuredapproximately 200 µS after theaperture measurement, thefluorescence signal (OFL) ismeasured simultaneously with theFSL.
RET Calibrators	None	Same
RET Controls	ABX Minotrol Retic	Same
RET Technicalparameters	MFIPIC	Same
RET Performance Claims
Carryover	RET% Carryover <1.0%RET# Carryover <1.0%	Same
Sample stability	For RET# and RET%:48H at 4°C	Same

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Item	ABX PENTRA DX 120 (K991839)Predicate Device for RETparameters	PENTRA XLRModified device
Intended Use	The ABX PENTRA DX 120Hematology Analyzer is anautomated hematology analyzerproviding complete blood count(CBC), differential leucocyte count(DIFF) as well as reticulocyte count(RET) and nucleated red blood cellcount (NRBC) for the in vitrodiagnostic use in clinicallaboratories.The clinical use of the reticulocytecount, specifically the immaturereticulocyte fraction (IRF) is tomonitor erythropoietic activity inpatients.	The PENTRA XLR is a quantitativemulti-parameter, automatedhematology analyzer for in vitrodiagnostic use in clinical laboratoriesto identify and enumerate thefollowing parameters: WBC, RBC,HGB, HCT, MCV, MCH, MCHC,RDW, PLT, MPV, LYM#, LYM%,MON#, MON%, NEU#, NEU%,EOS#, EOS%, BAS#, BAS%, aswell as the Reticulocyte parametersRET#, RET%, CRC, and IRF inK2EDTA and K3EDTAanticoagulated venous whole bloodsamples from patients ≥18 years ofage.RET mode: 35 μL
Specimen volume	Manual cycle: 130μLAutomatic cycle: 200μL
Throughput	120 samples / hour	80 samples / hour
Dimensions(Height x Widthx Depth)	75cm x 167cm x 55cm	82cm x 57cm x 54cm
Weight	110 kg	57 kg
RET Performance Claims
Precision/Reproducibility	No precision limits were claimed.Precision studies were done withcontrol material only.	Repeatability limit claims (in %)(for Low, Medium, High Levels ofblood samples):

	Within-run precision (in %):
	Param	Low	Med.	High	Param	Low	Med.	High
	RET%	6.9	2.5	3.1	RET%	N/A	12	8
	RET#	6.6	3.1	3.4	RET#	N/A	20	10
	CRC	6.7	3.1	3.4	CRC	18	15	10
	IRF	N/A	N/A	N/A	IRF	SD<0.04	25	15
	Between-day precision (in %):
	Reproducibility (for Low, Medium,High Levels of controls):
	Param	Low	Med.	High	Param	Low	Med.	High
Item	ABX PENTRA DX 120 (K991839)Predicate Device for RETparameters				PENTRA XLRModified device
	RET%	6.3	2.1	1.0		RET%	18	10	8
	RET#	6.3	2.0	1.0		RET#	18	10	8
	CRC	6.5	3.0	1.1		CRC	15	12	10
	IRF	N/A	N/A	N/A		IRF	18	10	8
Linearity / AMR	RET%: 0.9 – 33.7 (%)RET#: 0.026 – 1.081 (x106/mm3)					RET%: 0.7 – 27 (%)RET#: 0.01 – 0.5 (x106/mm3)
Accuracy(Methodcomparison)	n=200 patient samplesRET% r=0.96488RET# r=0.94224					n=300 patient samples minimumRET% r2>0.95RET# r2>0.95
Referenceintervals	RET% (%):Age 4-99 m/f: 0.5 – 2.5Age 14-19 m/f: 0.5 – 2.0Age 20-29 m/f: 0.6 – 2.0Age 30-99 m/f: 0.6 – 2.5					RET% (%):Age > 18 f: 0.70 – 2.35Age > 18 m: 0.70 – 2.06
	RET# (x106/mm3)Age 4-13 m: 0.03 – 0.12Age 4-13 f: 0.03 – 0.12Age 14-19 m: 0.03 – 0.09Age 14-19 f: 0.03 – 0.11Age 20-29 m: 0.03 – 0.10Age 20-29 f: 0.03 – 0.10Age 30-99 m: 0.03 – 0.13Age 30-99 f: 0.03 – 0.12					RET# (x106/mm3)Age > 18 f: 0.022 – 0.106Age > 18 m: 0.024 – 0.106
	CRC (%):Age 4-13 m: 0.50 – 1.64Age 4-13 f: 0.58 – 2.38Age 14-19 m: 0.52 – 1.74Age 14-19 f: 0.57 – 2.22Age 20-29 m: 0.70 – 2.07Age 20-29 f: 0.56 – 1.97Age 30-99 m: 0.70 – 2.66Age 30-99 f: 0.55 – 2.50					CRC (%):Age > 18 f: 0.44 – 2.27Age > 18 m: 0.51 – 2.15
	IRF: Not available					IRF:Age > 18 f: 0.018 – 0.191Age > 18 m: 0.033 – 0.232
Analyticalsensitivity	Not available					LoQ:RET% (%): 0.7RET# (x106/mm3): 0.01

7.3 Comparison with predicate Device : Differences

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SECTION 007 : 510(k) Summary

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SECTION 007 : 510(k) Summary

Item	ABX PENTRA DX 120 (K991839)Predicate Device for RETparameters	PENTRA XLRModified device
Sample stability	No claim when samples are stored atroom temperature	24h at Room Temp. for RET%,RET#, CRC and IRF

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8.0 Special Control/Guidance Document Referenced :

8.1 Standards Followed

CLSI EP05-A2: Evaluation of Precision Performance of Quantitative Measurement ● Methods - 2004
CLSI EP06-A: Evaluation of the Linearity of Quantitative Measurement Procedure: A ● Statistical Approach - 2003
CLSI EP07-A2: Interference Testing in Clinical Chemistry - 2005
CLSI EP09-A3: Measurement Procedure Comparison and Bias Estimation Using Patient Samples - 2013
. CLSI EP17-A2: Evaluation of Detection Capability for Clinical Laboratory Measurement Procedures - 2012
CLSI EP28-A3c: Defining, Establishing and Verifying Reference Intervals in the Clinical Laboratory - 2008
CLSI H26-A2: Validation, Verification and Quality Assurance of Automated Hematology Analyzers - 2010
CLSI H44-A2: Methods for reticulocyte Counting (Automated Blood Cell Counters, ● Flow Cytometry, and Supravital Dyes); Approved Guideline - Second Edition - 2004
IEC61010-1, IEC61010-2-081, IEC61010-2-101, UL61010-1, CAN/CSA-C22.2 No. ● 61010-1-12, CAN/CSA-C22.2 No. 61010.2.081-04, CAN/CSA-C22.2 No. 61010-2-101-04: Safety requirements for electrical equipment for measurement, control, and laboratory use
EN61326-1, EN61326-2-6: Electrical equipment for measurement, control and laboratory use - EMC requirements
. EN60825-1: Safety of Laser products - Part 1: Equipment classification and requirements
ISO14971: Medical devices – Application of risk management to medical devices

8.2 FDA Guidances Followed

Guidance for Industry and FDA Staff : Format for Traditional and Abbreviated 510(k)s -● 2005
Final Guidance for Industry and FDA: Class II Special Controls Guidance Document: Premarket Notifications for Automated Differential Cell Counters for Immature or Abnormal Blood Cells - 2001
Guidance for Industry and FDA Staff : Guidance for the Content of Premarket ● Submissions for Software Contained in Medical Devices - 2005
Guidance for Industry, FDA Reviewers and Compliance on Off-The-Shelf Software Use ● in Medical Devices - 1999
Guidance for Industry and Food and Drug Administration Staff on the Content of Premarket Submissions for Management of Cybersecurity in Medical Devices - 2014

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9.0 Summary of Performance Data :

Note :

RET parameters included in this submission are the following:

. RET#
. RET%
CRC
IRF

RET# are calculated using RBC value.

The RBC value reported in the RET mode is obtained from a measurement identical to the existing RBC measurement on the ABX PENTRA 80.

The performance of the PENTRA XLR RBC parameter obtained in RET mode has been verified during the RET parameters validation. The RBC parameter performance is identical to the performance obtained in CBC mode and previously detailed to FDA through K024002.

9.1 Analytical Performance

9.1.1 Analytical Limits at Low Level

Limit of Blank (LoB) and Limit of Detection (LoD) studies cannot be performed for Reticulocyte parameters, because it is not possible to have result when there is no or not enough RBC in the sample. A verification of the LoB and LoD has been done for the RBC parameter.

Analytical sensitivity has been determined for the Reticulocyte parameters according to CLSI H44-A2 guideline. A verification of the LoQ according to CLSI EP17-A2 guideline has been done for the RBC parameter.

Limit of Blank (LoB)

Plasma samples, obtained by centrifugation of normal samples, were used as blank samples, in order to be as close as possible as the blood sample matrix.

To estimate the LoB, a total of 60 repeated measurements of different plasma are run in the same series (6 different samples run 10 times).

This test is performed on 2 PENTRA XLR instruments with two reagents lots.

RBC results on PENTRA XLR met specifications and are consistent with ABX PENTRA 80 claim.

LoB obtained from 60 repeated measurements of 6 different plasma samples, are:

Measurand	LoB
RBC	0 x 106/mm3

Limit of Detection (LoD)

A set of six samples with very low parameter concentration (i.e. in the range LoB and 4 x LoB) are run 10 times over several days.

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To estimate the LOD, take 60 results and calculate the pooled standard deviation (SDs). This test is performed on 2 PENTRA XLR instruments with two reagents lots. RBC results on PENTRA XLR met specifications and are consistent with ABX PENTRA 80 claim.

LoD obtained from 10 runs of 6 low samples on each instrument are:

Measurand	LoD
RBC	$0.01 x 10^6/mm^3$

Analytical sensitivity - Limit of Quantitation (LoQ)

For Reticulocyte parameters: ●

To estimate the analytical senstivity for Reticulocyte parameters, a range of linearity in low concentrations is prepared. 7 levels are prepared and run 4 times each. This test is performed on at least 3 PENTRA XLR instruments with four reagents lots.

The Analytical sensitivity data are considered acceptable when the distribution of the residuals is randomly distributed and r2 higher than 0.98. The lowest value obtained in agreement with the acceptance criteria is the sensitivity limit and will be used as low limit for measuring range.

Analytical sensitivity limits obtained are:

Measurand	Analytical sensitivity
RET%	0.7%
RET#	0.01 x 106/mm3

For RBC parameter: ●

To estimate the limit of quantitation, several ranges of linearity in low concentrations are prepared. Between 3 to 6 samples by level are prepared and run at least 5 times each, 40 replicates by level are necessary. The LoQ data are considered acceptable when the %Total-error is smaller than the desired total error for each measurand.

This test is performed on 2 PENTRA XLR instruments with two reagents lots.

RBC results on PENTRA XLR met specifications and are consistent with ABX PENTRA 80 claim.

LoQ obtained from at least 40 runs of 4 samples by level are:

Measurand	LoQ
RBC	$0.24 \times 10^{6}/mm^{3}$

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9.1.2 Precision(Repeatability/Reproducibility) Imprecision (Repeatability)

Repeatability was performed using a minimum of 10 normal and 5 abnormal fresh whole blood samples collected into tubes containing K2EDTA anticoagulant, at 3 different clinical sites. Each sample was run 12 consecutive times on the PENTRA XLR, in a single day and all runs were completed within 8 hours of sample collection.

The size of the standard deviation (SD) was compared with the mean value of each parameter. This standard deviation divided by the mean is known as the Coefficient of Variation (CV) and is expressed as a percentage: CV% = (100*[Standard Deviation/Mean])

The results obtained were in the specifications. RBC results are consistent with ABX PENTRA 80 claim.

Parameter	Low level		Normal Level		High Level
	Claim	Level	Claim	Level	Claim	Level
RET% (%)	Not applicable		CV%<12	0.5 - 3	CV%<8	> 3
RET#(10 6/mm³)	Not applicable		CV%<20	0.02 - 0.1	CV%<10	> 0.1
CRC (%)	Not applicable		CV%<15	0.75 - 2.3	CV%<10	> 2.3
IRF	SD < 0.04	< 0.15	CV%<25	0.15 - 0.30	CV%<15	> 0.30
RBC(10 6/mm³)	CV% < 2.5	1.5 - 4	CV%<2.0	4 - 6	CV%<1.5	> 6

Precision (Repeatability) Acceptance Criteria

Imprecision (Reproducibility)

Reproducibility was assessed on four PENTRA XLR instruments at four different sites, each with its own operator. On each site; High, Normal, and Low levels of one single lot of control material (Minotrol Retic for the Reticulocyte parameters Difftrol for the RBC parameter) were run in duplicate, twice each day, during a minimum of 25 days.

Total standard deviation and CV% were calculated for each measurand and results obtained were in the specifications. RBC results are consistent with ABX PENTRA 80 claim.

Minotrol Retic
Parameter	Low Level Control		Normal Level Control		High Level Control
	CV within-run	CV total	CV within-run	CV total	CV within-run	CV total
RET%	15%	18%	6%	10%	7%	8%
RET#	10%	18%	10%	10%	7%	8%
CRC	10%	18%	8%	10%	5%	8%
IRF	10%	15%	5%	12%	3%	10%
RBC	2%	3%	2%	3%	2%	3%
Difftrol
Parameter	Low Level Control		Normal Level Control		High Level Control
	CV within-run	CV total	CV within-run	CV total	CV within-run	CV total
RBC	2.0%	3.0%	1.5%	2.5%	1.2%	2.5%

Precision (Reproducibility) Acceptance Criteria

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Linearity / Assay's Measuring (Reportable) Range 9.1.3

Commercial Linearity kits were used to perform the linearity studies. The expected values of the kit samples were considered the "true values". Each level was run in replicates of four (n=4) as recommended by the kit supplier. For each level, the 4 replicate results wersus the theoretical value. The findings of the polynomial regression analysis indicate that the PENTRA XLR exhibits linearity across the claimed range.

The Analytical Measuring Range is defined as the range comprised between the Analytical Limit or Limit of Quantitation and the High Linearity Limit determined for each parameter. The claimed AMR are therefore:

Parameter	AMR on PENTRA XLR
RET% (%)	0.7 - 27
RET# (106/mm3)	0.01 - 0.5
RBC (106/mm3)	0.2 - 8.0

RBC results are consistent with ABX PENTRA 80 claim.

9.1.4 Carryover

The potential for sample carryover was tested in duplicate on the PENTRA XLR instrument using alternating high and low concentrations samples.

The percentage of carryover is calculated using the formula below:

$$Ct,% = \frac{low,,4-low,,6}{high,,3-low,,6} \times 100$$

All carry-over results are within specifications for the PENTRA XLR System. RBC results are consistent with ABX PENTRA 80 claim.

	Carry-over Limit(%CV)
RBC	<2%
RET%	<1%
RET#	<1%

Interfering substances 9.1.5

The interference effect is evaluated following two methodologies:

By addition : evaluating the effect of potentially interfering substances added to the sample of interest:
A 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.

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For all tests performed with the following potential interferents, the bias remained below the acceptable limit and therefore, no significant interference was observed: urea, bilirubin, lipemia, and hemolysis.

-By comparison: evaluating the bias of individual specimen:
Representative patient specimens (with known or potential reticulocyte interferents, as given in CLSI H44-A2 guidance document) and control samples (without interferent) are run in duplicate in comparison to a comparative measurement procedure (ABX PENTRA DX 120). Then the bias versus comparative measurement values was plotted for each specimen group. Both measurement procedures had 10 to 20 samples in each group to demonstrate sufficient precision. A comparable effect was observed on the PENTRA XLR and the reference device for the interferences from: Abnormal RBC, Basophilic stippling, Cold agglutinins, Giant platelets, Hemolysis, Howell-Jolly Bodies, Leukocyte fragments, Nucleated erythrocytes, Pappenheimer bodies, Paraproteins, Platelet clumps, Platelet/erythrocyte coincidence.

Additionally, Heinz Bodies, Parasites and Autofluorescence are potential interferents on respectively WBC and Monocytes counts that could not be tested, but that are well described in literature.

9.1.6 Sample stability

10 whole venous blood specimens (collected in K2EDTA) were analyzed on the PNTRA XLR at one site in US. Following the collection (TO), each specimen was divided in half, with one sample stored at ambient temperature (24°C) and the other stored under refrigerated conditions (4℃). Testing for stability was performed at 1, 2, 3, 4, 6, 8, 24, 48 and 72 hours after T0 When sufficient volume is available, each time point is tested in duplicate. The acceptance criteria for sample stability is given as an acceptable maximum bias of the value at T with the value at T0. All data passed specifications. RBC results are consistent with ABX PENTRA 80 claim.

Parameters	Sample stability when stored refrigerated (2-8°C)	Sample stability when stored at room temperature (20-24°C)
RET%	48 hours	24 hours
RET#	48 hours	24 hours
CRC	48 hours	24 hours
IRF	48 hours	24 hours
RBC	48 hours	48 hours

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9.2 Other supportive performance data using clinical specimens

In order to support the equivalence and comparability claims made for the PENTRA XLR in vitro diagnostic hematology analyzer, some performance studies were done in external clinical laboratories with clinical blood specimens collected prospectively or not. These may be considered as "Clinical studies".

9.2.1 Comparability with Predicate Device

A total of 376 whole blood specimens (collected in K2EDTA) from adult patients were analyzed at three test sites in the US. Different instruments and operators were used at each site.

Each of the samples was analyzed in duplicate on the PENTRA XLR and on the predicate ABX PENTRA DX 120.

Bias was estimated at three points for each reticulocyte parameter: the low end of the distribution of observations, the mid-point, and the high end of the distribution. Bias was estimated separately for each replicate. Acceptance criteria were met for all measurands at all levels. These findings support the claim that the PENTRA XLR candidate device and the ABX PENTRA DX 120 predicate device are substantially equivalent, and demonstrate acceptable levels of bias.

9.2.2 Comparability between Anticoagulant types

A total of 90 normal and pathological blood specimens were analyzed on the PENTRA XLR at two sites in the US. Different instruments and operators were used at each site. The specimens used in this study were venous blood specimens that were prospectively collected for this study specifically. Each subject provided blood collected in both K2EDTA and K3EDTA.

Each of the samples was analyzed in duplicate on the PENTRA XLR.

Bias was estimated at three points for each reticulocyte parameter: the low end of the distribution of observations, the mid-point, and the high end of the distribution. Bias was estimated separately for each replicate. Acceptance criteria were met for all measurands at all levels. These findings support the claim that K2EDTA and K3EDTA specimens give comparable results as measured on the PENTRA XLR hematology analyzer.

9.2.3 Comparability between CBC and RET modes for RBC

A total of 107 normal and pathological blood specimens were analyzed on two PENTRA XLR instruments at one site in France. The specimens used in this study were venous blood specimens collected in K2EDTA.

Each subject specimen was analyzed in duplicate on both instruments in RET mode and CBC mode.

Bias was estimated at three points for RBC parameter: the low end of the distribution of observations, the mid-point, and the high end of the distribution. Bias was estimated separately for each replicate. Acceptance criteria were met at all levels. These findings support the claim that CBC and RET modes give comparable RBC results as measured on the PENTRA XLR hematology analyzer.

9.2.4 Reference Interval

242 (122 female and 120 male) normal adult samples (whole blood samples collected in K2EDTA) were analyzed in duplicate on the PENTRA XLR at two test sites in the US.

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The nonparametric data analysis method was used, depending only on the ranks of the reference data arranged in order of increasing size. Per EP28-A3, the reference interval is determined to be between and including the lower and upper reference limits, which enclose 95% of the values from the reference population subjects. Confidence intervals for the reference limit were calculated using a 90% probability (90% CI).

For each gender, a reference interval has been defined as described in the following table.

PENTRA XLR	FEMALES(N=122)		MALES(N=120)
Reference Interval	LOW	HIGH	LOW	HIGH
RET%	0.70	2.35	0.70	2.06
RET#	0.022	0.106	0.024	0.106
CRC	0.44	2.27	0.51	2.15
IRF	0.018	0.191	0.033	0.232

These intervals are given in the labeling of the PENTRA XLR.

However, expected values will vary with sample population and/or geographical location. Horiba highly recommends that each laboratory establishes its own normal ranges based upon its local population.

Proposed Labeling : 10.0

The labeling is written as per the recommendations given in standard EN18113-2. It takes into account the requirements of 21 CFR Part 809.10.

11.0 Conclusion :

As per 21CFR Part §807.92(b)(3), the nonclinical tests demonstrate that the PENTRA XLR device is as safe, as effective, and performs as well as or better than the predicate device .

The submitted information in this premarket notification is complete and supports a substantial equivalence decision.

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.”