Predicate Devices

Reference Devices

AI/ML (Artificial Intelligence / Machine Learning)

No
The document mentions "machine vision algorithms" for image analysis, which is a form of computer vision. While computer vision can be a component of AI/ML systems, the description does not explicitly state the use of AI or ML for tasks like classification, prediction, or learning from data. The analysis is described as resembling traditional blood smear and hemocytometer counting, which typically relies on predefined rules and algorithms rather than learned models.

Therapeutic

No.
The device is an in vitro diagnostic (IVD) device used for analysis of blood parameters, and its intended use is for diagnosis and monitoring of diseases, not for therapy or treatment.

Diagnostic

Yes

Explanation: The HemoScreen is described as an "automated hematology analyzer intended for the enumeration and classification of ... parameters in capillary and venous whole blood" and is for "in vitro diagnostic use." It performs a complete blood count (CBC) with differential, which is a common diagnostic test used to detect a wide range of conditions from anemia to infections and blood cancers. The device produces results (20 common CBC parameters) that are used by clinicians to make diagnostic decisions.

SaMD (Software as a Medical Device)

No

The device description explicitly states that the HemoScreen is a "tabletop device" (hardware) that uses a "disposable reagent cartridge" and a "disposable sampler" (hardware components). While it uses software for image analysis, it is fundamentally a hardware-based system.

IVD (In Vitro Diagnostic)

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

Here's why:

Intended Use Statement: The "Intended Use / Indications for Use" section explicitly states: "The HemoScreen is for in vitro diagnostic use in clinical laboratories and/or POC settings..."
Nature of the Test: The device analyzes blood samples (capillary and venous whole blood) to enumerate and classify various hematological parameters (WBC, RBC, HGB, etc.). This is a classic example of an in vitro diagnostic test, as it involves examining biological samples outside of the body to provide information about a person's health status.
Device Description: The description details how the device processes blood samples with reagents in a disposable cartridge, captures images, and analyzes them to produce diagnostic results. This process is consistent with in vitro diagnostic testing.
Performance Studies: The provided performance studies (Limit of Blank, LoD, LoQ, Linearity, Repeatability, Reproducibility, Interference, Stability, Method Comparison, Flagging, Reference Intervals, Vein to Capillary Equivalency) are all standard types of studies conducted to validate the performance of an in vitro diagnostic device.
Predicate Device: The mention of a predicate device (Sysmex XN Series, K112605) which is a known hematology analyzer, further confirms that the HemoScreen is intended for the same diagnostic purpose.

Therefore, based on the provided information, the HemoScreen clearly falls under the definition of an In Vitro Diagnostic device.

PCCP (Predetermined Change Control Plan) Authorized

N/A

Overview

Intended Use / Indications for Use

The HemoScreen is a point-of-care (POC) automated hematology analyzer intended for the enumeration and classification of the following parameters in capillary and venous whole blood (K2EDTA anticoagulated): WBC, RBC, HGB, HCT, MCV, MCH, MCHC, RDW, PLT, MPV, NEUT%, NEUT#, LYMP%, LYMP#, MONO%, MONO#, E0%, E0%, BASO %, and BASO#. The HemoScreen is for in vitro diagnostic use in clinical laboratories and/or POC settings for adults and children at least 2 years of age.

Product codes

GKZ

Device Description

HemoScreen is a point of care (POC), automated hematology analyzer that provides 20 common CBC parameters, including a 5-part leukocyte (WBC) differential, in capillary and venous whole blood samples. The HemoScreen analyzer (reader) is a tabletop device that is designed to use with a disposable reagent cartridge. In addition to the cartridge, the system includes a disposable sampler with two glass capillaries which is used to collect the blood sample and then transfer it to the cartridge.

Once the cartridge is inserted into the reader, there are no further procedural steps; blood is expelled from the capillaries (sampler) into the reagent compartments (cartridge). The reader then mixes the blood sample with the reagents by alternately pressing compressible portions of the cartridge, eventually causing the suspension of cells to flow into the microfluidic chamber. Cells flowing in the microfluidic chamber focus into a single-cell plane due to a patented physical phenomenon known as viscoelastic focusing.

The reader then captures images of the focused cells and analyzes them in real time using machine vision algorithms. When analysis is complete, the results are displayed to the user on the reader's touch screen and may be printed to an adjacent printer or exported to a USB flash drive. The cartridge is ejected by the analyzer after analysis, and can then be safely disposed of, as the reagents and blood sample remain within the cartridge.

The basic staining and microscopic image analysis performed by HemoScreen closely resembles the traditional blood smear and the hemocytometer counting chamber. Leukocytes are classified based on their staining properties and morphology, whereas absolute counts are obtained by counting the cells contained in a chamber of predetermined volume. Test results are obtained within six (6) minutes and the results are saved.

Quality Control: Commercial 3-level liguid quality controls, PIX-CBC Hematology Controls, are recommended for use with the HemoScreen. These controls cover all the tested parameters and are sampled the same way whole blood is sampled.

Software: The HemoScreen software displays an intuitive, simple-to-use user interface that is operated via the touch screen. The software is responsible for operating the device, performing the measurements, and recording the results.

Mentions image processing

The reader then captures images of the focused cells and analyzes them in real time using machine vision algorithms.

The basic staining and microscopic image analysis performed by HemoScreen closely resembles the traditional blood smear and the hemocytometer counting chamber. Leukocytes are classified based on their staining properties and morphology, whereas absolute counts are obtained by counting the cells contained in a chamber of predetermined volume.

Mentions AI, DNN, or ML

Not Found.

Input Imaging Modality

Microscopic images

Anatomical Site

Not Found.

Indicated Patient Age Range

Adults and children at least 2 years of age.

Intended User / Care Setting

In vitro diagnostic use in clinical laboratories and/or POC settings.

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

Method Comparison & Clinical Sensitivity/Specificity

Sample Size: 495 normal and pathological residual whole blood specimens collected across three clinical sites.
Data Source: Residual whole blood specimens.
Annotation Protocol: Each sample analyzed twice on the HemoScreen (first usable replicate result used for data analyses) by operators resembling intended users. Analyzed twice on the predicate by laboratory personnel (comparative results averaged for data analyses). Three blood film slides prepared for each sample for measurement by an automated blood smear (differential) method (2 slides/200 cells counted per slide for a total of 400 cell differential according to CLSI H20-A2). Experienced operators trained to use the automated blood smear performed the differentials, including morphology evaluation, and results were verified.
BASO Study: 95 whole blood samples, focusing on high basophil levels. Analyzed by HemoScreen, light microscopy (for %basophils), and Sysmex method (for absolute counts).

Flagging

Sample Size: 402 whole blood specimens.
Data Source: Whole blood specimens.
Annotation Protocol: Compared HemoScreen WBC flagging rate to predicate WBC differential results and blood smears. Evaluated two types of abnormalities: distributional and morphological. Predictive value tables created for distributional and morphological classifications, separately and combined, according to CLSI H20-A2.

Reference Intervals- Adult Males and Females (CLSI EP28-A3C)

Sample Size: Minimum of 120 male subjects and 120 female subjects (Actual: 123 female, 120 male).
Data Source: Freshly collected K2EDTA venous blood from healthy (self-reported) adult (19-69 years old) male and female volunteers.
Annotation Protocol: Each blood sample analyzed by HemoScreen in one replicate. Reference intervals calculated in accordance with CLSI standard EP28-A3C; namely, 95% distribution-free reference intervals (male and female) identified per parameter, based on the 2.5th and 97.5th percentiles of each variable.

Vein to Capillary Equivalency

Sample Size: 75 normal and pathological paired capillary and venous whole blood specimens.
Data Source: Paired capillary and venous whole blood specimens drawn from volunteer subjects across three clinical sites.
Annotation Protocol: Each venous and capillary specimen assayed once on the HemoScreen by intended users, twice on the predicate by laboratory personnel. Samples also measured by an automated blood smear method (2 slides/200 cells counted per slide for a total of 400 cells) by experienced operators who also verified results. Capillary whole blood results from HemoScreen compared to venous whole blood results from HemoScreen and capillary whole blood results from the comparative method.

Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)

Nonclinical Data

Limit of Blank (LoB)

Study Type: Analytical performance study.
Sample Size: Five residual normal venous blood samples, assayed six times on two HemoScreen devices, using three cartridge and sampler batches (60 measurements per parameter).
Key Results: LoB for WBC, RBC, HGB, HCT, and PLT determined to be 0.0 for all.

Limits of Detection (LoD) and Quantitation (LoQ)

Study Type: Analytical performance study.
Sample Size: Five residual blood samples processed to low target concentration, assayed six times on each of two HemoScreen devices (60 runs total) using six cartridge batches and eight sampler batches.
Key Results: LoD and LoQ values provided for WBC, RBC, HGB, HCT, and PLT. All TE goals met.

Linearity

Study Type: Analytical performance study.
Sample Size: Six venous whole blood samples manipulated to create linearity panels. Seven concentrations for RBC, HGB, HCT; 10 for PLT; 14 for WBC. Each level tested in duplicate on two HemoScreen analyzers.
Key Results: Analytical Measurement Interval (AMI) ranges established for WBC (0.5-80.0), RBC (1.0-8.8), HGB (3.0-25.0), HCT (9.0-78.0), and PLT (20-800).

Repeatability (Internal and External Operators)

Study Type: Short-term precision study.
Sample Size:
- Internal Operators: 14 venous whole blood specimens (5 normal, 9 pathological), tested 15 times by HemoScreen.
- External Operators: Minimum of 12 blood samples per site (across 3 clinical sites), assayed 15 times.
Key Results:
- Internal Operators: CVs ranged from 0.2% (RDW) to 23.9% (EOS#). Basophil CVs stated as NA.
- External Operators: CVs ranged from 0.5% (MCV) to 33.2% (EOS%). Basophil CVs stated as NA.
- Performance shown to be in-line between internal and external operators, and predefined acceptance criteria were met for all 20 measurands.

Reproducibility

Study Type: Multi-site precision study.
Sample Size: A 3-level control set (low, normal, high) assayed at three sites for 5 days. One run per day, with five replicates per run, for a total of 25 measurements per site and level. Total 225 measurements per measurand.
Key Results: Provided within-day, between-day, between-site, and overall reproducibility (SD and CV%) for all 20 parameters across low, normal, and high control levels. Overall CV% ranges from 0.6% (MCV) to 20.4% (EOS%).

Interference

Study Type: Analytical interference study.
Sample Size:
- Lipemia: 11 blood sample remnants.
- Bilirubin: 3 blood samples manipulated with exogenous bilirubin.
- Leukocytosis: 9 blood samples with high WBC levels (>50x103/uL).
- Thrombocytosis: 8 blood samples with high PLT levels (>700x102/uL).
- NRBC flagged samples: 9 samples.
Key Results: No significant bilirubin interference up to 50 mg/dL for WBC, HGB, RBC, HCT, MCV, MCH, MCHC, RDW; up to 30 mg/dL for PLT and MPV. No interference from high triglyceride levels (319-729 mg/dL), high WBC (up to 317x103/uL), high PLT (up to 2,045x103/uL), or NRBCs.

Whole Blood Stability

Study Type: Analytical stability study.
Sample Size: 18 freshly collected venous whole blood samples from volunteer subjects.
Key Results: Performance at all time points (2, 6, 7, and 8 hours) and for all parameters met acceptance criteria. Validated that venous blood samples stored at room temperature can be analyzed for seven (7) hours from collection without compromising performance.

Clinical Data

Method Comparison & Clinical Sensitivity/Specificity

Study Type: Method Comparison.
Sample Size: 495 normal and pathological residual whole blood specimens. Separately, 95 whole blood samples with high basophil levels (BASO Study).
Key Results:
- High Pearson Correlation Coefficients (r) for most parameters when compared to Sysmex and Blood Smear. Most correlation values were above 0.9, with some exceptions like MCHC (0.675 vs Sysmex), MON (0.718 vs Sysmex, 0.594 vs Blood Smear).
- 95% confidence intervals for mean bias / mean relative bias were within acceptance limits for all parameters, for both comparators, with or without flags (except for MON#, MON% where flagged results were excluded for correlation point estimate to meet acceptance limit).
- Basophil data (BASO Study): r=0.484 vs Sysmex for absolute count, and r=0.725 vs Blood Smear for %.

Flagging

Study Type: Diagnostic accuracy.
Sample Size: 402 whole blood specimens.
Key Results:
- Overall WBC Flagging (HemoScreen vs Predicate): PPA=95.9%, NPA=82.1%, Overall Agreement=92.3%.
- Overall WBC Flagging (HemoScreen vs Blood Smear): PPA=93.8%, NPA=71.7%, Overall Agreement=87.6%.

Reference Intervals

Study Type: Reference interval establishment.
Sample Size: 123 female subjects, 120 male subjects.
Key Results: HemoScreen reference intervals (Lower and Upper Limits) provided for all 20 parameters for both male and female populations.

Vein to Capillary Equivalency

Study Type: Specimen equivalency study.
Sample Size: 75 normal and pathological paired capillary and venous whole blood specimens.
Key Results:
- 95% confidence intervals for mean bias / mean relative bias were within acceptance limits for all 20 parameters, against all comparators, with and without flags.
- For MON%, the point estimate of the correlation between capillary and blood smear capillary met acceptance limit when flagged results were excluded. For other parameters, correlation point estimates met acceptance criteria.
- Demonstrated comparable performance characteristics for capillary and venous whole blood specimens.

Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)

Flagging:

Diagnostic Accuracy - Overall WBC Flagging, HemoScreen versus Predicate:
- PPA: 95.9% (95% CL: 93.0%-97.9%)
- NPA: 82.1% (95% CL: 73.4%-88.8%)
- Overall Agreement: 92.3% (95% CL: 89.2%-94.7%)
Diagnostic Accuracy - Overall WBC Flagging, HemoScreen versus Blood Smear:
- PPA: 93.8% (95% CL: 90.3%-96.3%)
- NPA: 71.7% (95% CL: 62.4%-79.8%)
- Overall Agreement: 87.6% (95% CL: 83.9%-90.6%)

Predicate Device(s)

K112605

Reference Device(s)

Not Found.

Predetermined Change Control Plan (PCCP) - All Relevant Information

Not Found.

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

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Image /page/0/Picture/0 description: The image contains the logos of the Department of Health and Human Services and the Food and Drug Administration (FDA). The Department of Health and Human Services logo is on the left and consists of a stylized emblem. The FDA logo is on the right and includes the letters "FDA" in a blue square, followed by the words "U.S. FOOD & DRUG ADMINISTRATION" in blue text.

October 29, 2018

PixCell Medical Technologies, Ltd. % Erika Ammirati Regulatory Consultant Erika B. Ammirati, RAC, MT (ASCP) 575 Shirlynn Court Los Altos, California 94022

Re: K180020

Trade/Device Name: HemoScreen Hematology Analyzer Regulation Number: 21 CFR 864.5220 Regulation Name: Automated differential cell counter Regulatory Class: Class II Product Code: GKZ Dated: December 28, 2017 Received: January 2, 2018

Dear Erika Ammirati:

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. 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 located 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.

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

1

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 803) for devices or postmarketing safety reporting (21 CFR 4, Subpart B) for combination products (see https://www.fda.gov/CombinationProducts/GuidanceRegulatoryInformation/ucm597488.html; 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 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

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

For comprehensive regulatory information about mediation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/) and CDRH Learn (http://www.fda.gov/Training/CDRHLearn). 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 (http://www.fda.gov/DICE) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).

Sincerely,

Leonthena R. Carrington -S

Lea Carrington Director Division of Immunology and Hematology Devices Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health

Enclosure

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Indications for Use

510(k) Number (if known)

Device Name HemoScreen Hematology Analyzer

Indications for Use (Describe)

The HemoScreen is a point-of-care (POC) automated hematology analyzer intended for the enumeration and classification of the following parameters in capillary and venous whole blood (K2EDTA anticoagulated): WBC, RBC, HGB, HCT, MCV, MCH, MCHC, RDW, PLT, MPV, NEUT%, NEUT#, LYMP%, LYMP#, MONO%, MONO#, E0%, E0%, BASO %, and BASO#. The HemoScreen is for in vitro diagnostic use in clinical laboratories and/or POC settings for adults and children at least 2 years of age.

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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510(k) SUMMARY

This summary of 510(k) safety and effectiveness information is being submitted in accordance with the requirements of SMDA 1990 and 21 CFR 807.92. The assigned 510(k) number is K180020.

807.92 (a)(1): Name:	PixCell Medical Technologies, Ltd.
Address:	6 Hayezira St.
Yoknaem Ilit, Israel 2069202
Phone:	+972-4-9593516
Email:	yaara@pixcell-medical.com
Contact:	Yaara Ben-Yosef, PhD

807.92 (a)(2): Device name- trade name and common name, and classification

Trade name: HemoScreen Hematology Analyzer

Common Name: Automated differential cell counter

Classification: 21 CFR 864.5220

807.92 (a)(3): Identification of the legally marketed predicate devices

Sysmex XN Series (Sysmex America, Inc, Lincolnshire, IL), cleared under K112605

807.92 (a)(4): Device Description

HemoScreen is a point of care (POC), automated hematology analyzer that provides 20 common CBC parameters, including a 5-part leukocyte (WBC) differential, in capillary and venous whole blood samples. The HemoScreen analyzer (reader) is a tabletop device that is designed to use with a disposable reagent cartridge. In addition to the cartridge, the system includes a disposable sampler with two glass capillaries which is used to collect the blood sample and then transfer it to the cartridge.

Once the cartridge is inserted into the reader, there are no further procedural steps; blood is expelled from the capillaries (sampler) into the reagent compartments (cartridge). The reader then mixes the blood sample with the reagents by alternately pressing compressible portions of the cartridge, eventually causing the suspension of cells to flow into the microfluidic chamber. Cells flowing in the microfluidic chamber focus into a single-cell plane due to a patented physical phenomenon known as viscoelastic focusing.

The reader then captures images of the focused cells and analyzes them in real time using machine vision algorithms. When analysis is complete, the results are displayed to the user on the reader's touch screen and may be printed to an adjacent printer or exported to a USB flash drive. The cartridge is ejected by the analyzer after analysis, and can then be safely disposed of, as the reagents and blood sample remain within the cartridge.

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The basic staining and microscopic image analysis performed by HemoScreen closely resembles the traditional blood smear and the hemocytometer counting chamber. Leukocytes are classified based on their staining properties and morphology, whereas absolute counts are obtained by counting the cells contained in a chamber of predetermined volume. Test results are obtained within six (6) minutes and the results are saved.

Quality Control: Commercial 3-level liguid quality controls, PIX-CBC Hematology Controls, are recommended for use with the HemoScreen. These controls cover all the tested parameters and are sampled the same way whole blood is sampled.

Software: The HemoScreen software displays an intuitive, simple-to-use user interface that is operated via the touch screen. The software is responsible for operating the device, performing the measurements, and recording the results.

807.92 (a)(5): Intended Use

The HemoScreen is a point-of-care (POC) automated hematology analyzer intended for the enumeration and classification of the following parameters in capillary and venous whole blood (K2EDTA anticoagulated): WBC, RBC, HGB, HCT, MCV, MCH, MCHC, RDW, PLT, MPV, NEUT%, NEUT#, LYMP%, LYMP#, MONO%, MONO#, EO%, EO#, BASO%, and BASO#. The HemoScreen is for in vitro diagnostic use in clinical laboratories and/or POC settings for adults and children at least 2 years of age.

807.92 (a)(6): Technological Similarities and Differences to the Predicate

The following chart describes similarities and differences between HemoScreen and the predicate.

| Comparison | HemoScreen | Sysmex
XN-Series (K112605) |
|------------------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Intended Use | Automated hematology analyzer | Same |
| Parameters
Measured | Red Blood Cells (RBC), White Blood Cells (WBC), Platelets (PLT), Hemoglobin (HGB), Hematocrit (HCT), Mean Corpuscular (erythrocyte) Volume (MCV), Mean Cell (erythrocyte) Hemoglobin (MCH), Mean Cell (erythrocyte) Hemoglobin Concentration (MCHC), Red Blood Cell Distribution Width (RDW)-CV Mean Platelets Volume (MPV), | Red Blood Cells (RBC), White Blood Cells (WBC), Platelets (PLT), Hemoglobin (HGB), Hematocrit (HCT), Mean Corpuscular (erythrocyte) Volume (MCV), Mean Cell (erythrocyte) Hemoglobin (MCH), Mean Cell (erythrocyte) Hemoglobin Concentration (MCHC), Red Blood Cell Distribution Width (RDW)-CV/SD Mean Platelets Volume (MPV), Neutrophils (NEUT; #/%), |
| Comparison | HemoScreen | Sysmex
XN-Series (K112605) |
| | • Monocytes (MONO; #/%),
• Lymphocytes (LYMP; #/%),
• Eosinophils (EO; #/%) and
• Basophiles (BASO; #/%) | • Lymphocytes (LYMP; #/%),
• Eosinophils (EO; #/%) and
• Basophiles (BASO; #/%)
• IG%/#,
• NRBC#/%,
• RET%/#,
• IPF, IRF,
• RET-He,
• WBC-BF, (Body fluids)
• RBC-BF, (Body fluids)
• MN%/#, (Body fluids)
• PMN%/#, (Body fluids)
• TC-BF (Body fluids) |
| Class | Class II | Same |
| Regulation
Number | 21 CFR 864.5220 | Same |
| Product Code | GKZ | Same |
| FDA Branch | Hematology | Same |
| Throughput | 10 samples/hour | 100 samples/hour maximum depending on mode
used |
| Test Principle | The HemoScreen uses a novel
focusing method called viscoelastic
focusing which causes the cells to
perfectly align into a plane. High
resolution microscopic images are
taken of the flowing cells. Each
image is analyzed using machine
vision algorithms and the different
cell types are differentiated and
counted. WBCs are stained prior to
analysis so as to enable
differentiation between their subtypes
and abnormal cells.
HGB is calculated based on the
optical density measured on intact
individual cells. | The XN Series performs analyses using the
following methods: fluorescence flow cytometry
and sheath flow DC detection. The first is used to
differentiate between WBC types and abnormal
cells while the second is used for RBC and PLT
analysis.
The HGB is measured using a standard
photometric method on the lysed RBC solution
which is reacted with SLS forming a colored
SLS-HGB complex. |
| Calibration | Factory calibrated | Requires operator calibrations |
| Sample Type | Anticoagulated whole blood | Same |
| Sample Volume | 40μL | 88 µL |

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807.92 (b)(1): Brief Description of Nonclinical Data

Limit of Blank- (Reference CLSI EP17-A2 and CLSI H26-A2)

Five residual normal venous blood samples (from both morphological and cell distribution aspects) were centrifuged to deplete the plasma supernatant of RBCs, WBCs and PLTs. These processed samples were separated to clean neutral tubes with no additives and were assayed six times on two HemoScreen devices for a total of 60 measurements per parameter, using three cartridge and sampler batches. The parameters under evaluation were WBC, RBC, HCT and PLT.

The limit of blank was determined by the 95th percentile of the distribution of the study variable, and the data are summarized below for all five parameters of interest.

Parameter	LoB
WBC	0.0 x 103/μL
RBC	0.0 x 106/μL
HGB	0.0 g/dL
HCT	0.0 %
PLT	0.0 x 103/μL

Summary Limit of Blank for WBC, RBC, HGB, HCT and PLT for the HemoScreen

Limits of Detection and Quantitation

For the LoDs and LoOs, five residual blood samples were processed to low target concentration, and measured by the comparative method. Each of the processed samples was assayed six times on each of the two HemoScreen devices (5 x 6 x 2 = 60 runs) using six cartridge batches and eight sampler batches. The LoDs were determined mathematically both from the LoBs and by HemoScreen testing.

The LoQs were defined as the lowest concentration in which pre-determined total error (TE) accuracy goals, as compared to the laboratory reference method, were satisfied. All TE goals were met (TEs were less than the goals), and the LoD and LoQ for the five parameters are shown below.

LoD and LoQ Summaries
Parameter	Units	LoD	LoQ
WBC	x 103/μL	0.20	0.51
RBC	x 106/μL	0.03	0.65
HGB	g/dL	0.11	1.87
HCT	%	0.28	5.66
PLT	x 103/μL	4.57	4.57

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Linearity (CLSI H26-A2 and CLSI EP6-A)

Six venous whole blood samples, with their respective results measured by the laboratory reference method, were manipulated to create the linearity panels for WBC, RBC, HGB, HCT, and PLT.

Seven concentrations were used for RBC. HGB and HCT, 10 concentrations were used for PLT, and 14 concentrations were used for WBC. Each concentration level was tested in duplicate on each of two HemoScreen analyzers. Scatter plots with linear fit (with 95% confidence intervals) of the observed value (Y =values measured on the HemoScreen) versus the expected value (X =calculated from the highest concentration of the HemoScreen result) were created. The HS data were evaluated for linearity by fitting a linear regression model and two polynomial regression models (quadratic and cubic) to the measurements. The linearity ranges are shown below.

Measurand	Final AMI
WBC (103/μL)	0.5-80.0
RBC (106/μL)	1.0-8.8
HGB (g/dL)	3.0-25.0
HCT (%)	9.0-78.0
PLT (103/μL)	20-800

Analytical Measurement Interval (AMI) Ranges

Repeatability (internal and external operators)

The short-term precision (repeatability) study was conducted in two parts; Part A evaluatedshortterm HemoScreen precision using normal and pathological fresh whole blood samples when testing was performed by PixCell employees (at a single external site); Part B evaluated short-term HemoScreen precision with the same sample types, but testing was performed across three clinical sites by external operators.

For the internal operators, a total of 14 venous whole blood specimens were tested 15 times by HemoScreen, including five samples that spanned the normal ranges, and nine samples with values outside the normal ranges for at least one of the following parameters: WBC. RBC. HCT. or PLT. The data was analyzed as instructed in CLSI EP05-A3.

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| Parameter | Target Range
(conventional units) | Mean
(conventional
units) | Repeatability
(SD) | CV |
|-----------|------------------ | WBC | 0.5-4.0 | WBC | >4.0-80.0 | RBC | 1.0-3.5 | RBC | >3.5-8.0 | HGB | 5-11 | HGB | >11-25 | HCT | 10-70 | MCV | 50-150 | MCH | 10-45 | MCHC | 26-38 | RDW | 10-40 | PLT | 20-150 | PLT | >150-800 | MPV | 7-25 | NEU# | WBC≤4.0x103/μL | NEU# | WBC>4.0x103/μL | LYM# | WBC≤4.0x103/μL | LYM# | WBC>4.0x103/μL | MON# | WBC≤4.0x103/μL | MON# | WBC>4.0x103/μL | EOS# | WBC≤4.0x103/μL | EOS# | WBC>4.0x103/μL | BAS# | WBC≤4.0x103/μL | BAS# | WBC>4.0x103/μL | NEU% | WBC≤4.0x103/μL | NEU% | WBC>4.0x103/μL | LYM% | WBC≤4.0x103/μL | LYM% | WBC>4.0x103/μL | MON% | WBC≤4.0x103/μL | MON% | WBC>4.0x103/μL | EOS% | WBC≤4.0x103/μL | EOS% | WBC>4.0x103/μL | BAS% | WBC≤4.0x103/μL | BAS% | WBC>4.0x103/μL --------------------|---------------------------------|-----------------------|-------|
| 2.79 | 0.138 | 4.9% |
| 12.60 | 0.504 | 4.0% |
| 3.22 | 0.038 | 1.2% |
| 4.98 | 0.073 | 1.5% |
| 8.52 | 0.186 | 2.2% |
| 13.73 | 0.219 | 1.6% |
| 40.79 | 0.639 | 1.6% |
| 82.43 | 0.413 | 0.5% |
| 26.49 | 0.221 | 0.8% |
| 31.89 | 0.311 | 1.0% |
| 14.98 | 0.037 | 0.2% |
| 116.07 | 3.277 | 2.8% |
| 270.88 | 9.371 | 3.5% |
| 10.75 | 0.172 | 1.6% |
| 1.31 | 0.077 | 5.8% |
| 5.57 | 0.350 | 6.3% |
| 0.98 | 0.078 | 8.0% |
| 5.92 | 0.300 | 5.1% |
| 0.34 | 0.060 | 17.8% |
| 0.86 | 0.135 | 15.7% |
| 0.10 | 0.025 | 23.9% |
| 0.25 | 0.033 | 13.5% |
| 0.00 | 0.005 | NA |
| 0.02 | 0.011 | NA |
| 48.82 | 2.418 | 5.0% |
| 50.01 | 1.900 | 3.8% |
| 36.39 | 2.235 | 6.1% |
| 39.61 | 1.385 | 3.5% |
| 11.52 | 1.970 | 17.1% |
| 9.93 | 1.353 | 13.6% |
| 3.60 | 0.888 | 24.7% |
| 2.25 | 0.427 | 19.0% |
| 0.17 | 0.198 | NA |
| 0.21 | 0.142 | NA |

Short-term Precision with Internal Operators

For the testing with external operators, a minimum of 12 blood samples per site were assayed 15 times and all 20 parameters were measured. A minimum of two HemoScreen analyzers were used at each site, and samples were assayed by at least two operators per site. The operators' job descriptions resembled those of the intended user profile in POC settings, and therefore included phlebotomists, laboratory assistants, nurses, and medical assistants.

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The blood samples at each site were selected based on their results obtained by the laboratory reference method. Sample selection was based on covering the analytical measurement ranges (AMRs), and the inclusion of medical decision points for WBC, RBC, HCT and PLT, with balanced distributions.

| Parameter | Target Range
(conventional units) | Mean
(conventional units) | SD | CV |
|-----------|--------------------------------------|------------------------------|--------|-------|
| WBC | 0.5-4.0 | 2.84 | 0.259 | 9.1% |
| WBC | 4.0-80.0 | 11.60 | 0.514 | 4.4% |
| RBC | 1.0-3.5 | 2.95 | 0.084 | 2.8% |
| RBC | 3.5-8.0 | 4.83 | 0.104 | 2.2% |
| HGB | 5-11 | 9.18 | 0.265 | 2.9% |
| HGB | 11-25 | 14.54 | 0.322 | 2.2% |
| HCT | 10-70 | 36.08 | 0.847 | 2.3% |
| MCV | 50-150 | 87.87 | 0.397 | 0.5% |
| MCH | 10-45 | 28.86 | 0.264 | 0.9% |
| MCHC | 26-38 | 32.81 | 0.339 | 1.0% |
| RDW | 10-40 | 16.05 | 0.076 | 0.5% |
| PLT | 20-150 | 84.60 | 6.033 | 7.1% |
| PLT | >150-800 | 317.32 | 11.067 | 3.5% |
| MPV | 7-25 | 11.22 | 0.213 | 1.9% |
| NEU# | WBC≤4.0x103/μL | 1.81 | 0.182 | 10.1% |
| NEU# | WBC>4.0x103/μL | 7.08 | 0.373 | 5.3% |
| LYM# | WBC≤4.0x103/μL | 0.69 | 0.095 | 13.7% |
| LYM# | WBC>4.0x103/μL | 3.49 | 0.277 | 7.9% |
| MON# | WBC≤4.0x103/μL | 0.26 | 0.056 | 21.3% |
| MON# | WBC>4.0x103/μL | 0.71 | 0.154 | 21.6% |
| EOS# | WBC≤4.0x103/μL | 0.06 | 0.019 | 31.9% |
| EOS# | WBC>4.0x103/μL | 0.30 | 0.047 | 15.5% |
| BAS# | WBC≤4.0x103/μL | 0.01 | 0.006 | NA |
| BAS# | WBC>4.0x103/μL | 0.01 | 0.009 | NA |
| NEU% | WBC≤4.0x103/μL | 62.07 | 2.551 | 4.1% |
| NEU% | WBC>4.0x103/μL | 63.20 | 2.102 | 3.3% |
| LYM% | WBC≤4.0x103/μL | 26.22 | 2.112 | 8.1% |
| LYM% | WBC>4.0x103/μL | 25.98 | 1.340 | 5.2% |
| MON% | WBC≤4.0x103/μL | 9.37 | 1.866 | 19.9% |
| MON% | WBC>4.0x103/μL | 7.59 | 1.442 | 19.0% |
| EOS% | WBC≤4.0x103/μL | 2.06 | 0.684 | 33.2% |
| EOS% | WBC>4.0x103/μL | 3.09 | 0.482 | 15.6% |
| BAS% | WBC≤4.0x103/μL | 0.28 | 0.263 | NA |
| BAS% | WBC>4.0x103/μL | 0.14 | 0.106 | NA |

Short-term Precision with External Operators

The all-sites data indicated that the predefined acceptance criteria were met for all the 20 measurands and in all tested ranges. Additionally, there were no distinct differences in performance observed among sites. Moreover, external operator precision testing demonstrated performance that is in-line with the performance that was shown when testing was done by PixCell employees.

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Reproducibility (CLSI EP05-A3 and H26-A2)

The study was conducted at each of three sites for a total of 5 days, during which time all 20 measurands were assayed using a 3-level control set comprising low, normal and high levels of measurands. Each site utilized different analyzers and batches of cartridges and samplers, and the same lot of controls. The tests were performed as follows: one run per day, with five replicates per run, for a total of 25 measurements per site and level. The total number of measurements for each measurand was 225. To further demonstrate precision performance SD and %CV of within-day, between-day, between-site and overall reproducibility were calculated per site and for the combined sites, as shown below.

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| | | | Within-Day
(Repeatability) | | Between-Day | | Between-Site | | Overall Reproducibility | |
|-----------|--------|--------|-------------------------------|-------|-------------|------|--------------|------|-------------------------|-------|
| Parameter | Level | Mean | SD | CV% | SD | CV% | SD | CV% | SD | CV% |
| WBC | Low | 2.82 | 0.203 | 7.2% | 0.000 | 0.0% | 0.116 | 4.1% | 0.234 | 8.3% |
| WBC | Normal | 8.98 | 0.424 | 4.7% | 0.078 | 0.9% | 0.234 | 2.6% | 0.490 | 5.5% |
| WBC | High | 20.62 | 0.802 | 3.9% | 0.219 | 1.1% | 0.355 | 1.7% | 0.904 | 4.4% |
| RBC | Low | 2.66 | 0.052 | 1.9% | 0.011 | 0.4% | 0.040 | 1.5% | 0.066 | 2.5% |
| RBC | Normal | 4.93 | 0.096 | 1.9% | 0.016 | 0.3% | 0.065 | 1.3% | 0.117 | 2.4% |
| RBC | High | 5.92 | 0.108 | 1.8% | 0.020 | 0.3% | 0.038 | 0.6% | 0.116 | 2.0% |
| HGB | Low | 7.01 | 0.168 | 2.4% | 0.049 | 0.7% | 0.045 | 0.6% | 0.181 | 2.6% |
| HGB | Normal | 15.48 | 0.430 | 2.8% | 0.078 | 0.5% | 0.075 | 0.5% | 0.444 | 2.9% |
| HGB | High | 22.04 | 0.469 | 2.1% | 0.076 | 0.3% | 0.073 | 0.3% | 0.481 | 2.2% |
| HCT | Low | 19.01 | 0.376 | 2.0% | 0.073 | 0.4% | 0.340 | 1.8% | 0.512 | 2.7% |
| HCT | Normal | 40.48 | 0.819 | 2.0% | 0.080 | 0.2% | 0.567 | 1.4% | 0.999 | 2.5% |
| HCT | High | 57.32 | 1.077 | 1.9% | 0.214 | 0.4% | 0.334 | 0.6% | 1.148 | 2.0% |
| MCV | Low | 71.42 | 0.438 | 0.6% | 0.000 | 0.0% | 0.506 | 0.7% | 0.669 | 0.9% |
| MCV | Normal | 82.19 | 0.526 | 0.6% | 0.000 | 0.0% | 0.273 | 0.3% | 0.593 | 0.7% |
| MCV | High | 96.90 | 0.486 | 0.5% | 0.116 | 0.1% | 0.280 | 0.3% | 0.573 | 0.6% |
| MCH | Low | 26.32 | 0.465 | 1.8% | 0.000 | 0.0% | 0.218 | 0.8% | 0.513 | 1.9% |
| MCH | Normal | 31.43 | 0.442 | 1.4% | 0.084 | 0.3% | 0.198 | 0.6% | 0.492 | 1.6% |
| MCH | High | 37.26 | 0.402 | 1.1% | 0.070 | 0.2% | 0.319 | 0.9% | 0.518 | 1.4% |
| MCHC | Low | 36.86 | 0.764 | 2.1% | 0.023 | 0.1% | 0.502 | 1.4% | 0.915 | 2.5% |
| MCHC | Normal | 38.24 | 0.648 | 1.7% | 0.111 | 0.3% | 0.312 | 0.8% | 0.727 | 1.9% |
| MCHC | High | 38.46 | 0.491 | 1.3% | 0.125 | 0.3% | 0.379 | 1.0% | 0.633 | 1.6% |
| RDW | Low | 13.80 | 0.114 | 0.8% | 0.000 | 0.0% | 0.112 | 0.8% | 0.160 | 1.2% |
| RDW | Normal | 16.57 | 0.072 | 0.4% | 0.000 | 0.0% | 0.129 | 0.8% | 0.148 | 0.9% |
| RDW | High | 13.79 | 0.193 | 1.4% | 0.097 | 0.7% | 0.180 | 1.3% | 0.281 | 2.0% |
| PLT | Low | 70.71 | 3.408 | 4.8% | 1.329 | 1.9% | 4.222 | 6.0% | 5.586 | 7.9% |
| PLT | Normal | 269.42 | 9.208 | 3.4% | 3.300 | 1.2% | 11.328 | 4.2% | 14.967 | 5.6% |
| PLT | High | 567.99 | 17.348 | 3.1% | 2.958 | 0.5% | 14.760 | 2.6% | 22.969 | 4.0% |
| MPV | Low | 9.91 | 0.084 | 0.8% | 0.000 | 0.0% | 0.057 | 0.6% | 0.101 | 1.0% |
| MPV | Normal | 9.82 | 0.069 | 0.7% | 0.014 | 0.1% | 0.051 | 0.5% | 0.087 | 0.9% |
| MPV | High | 9.98 | 0.062 | 0.6% | 0.004 | 0.0% | 0.051 | 0.5% | 0.080 | 0.8% |
| NEU# | Low | 1.48 | 0.120 | 8.1% | 0.010 | 0.7% | 0.043 | 2.9% | 0.128 | 8.6% |
| NEU# | Normal | 4.44 | 0.221 | 5.0% | 0.000 | 0.0% | 0.000 | 0.0% | 0.221 | 5.0% |
| NEU# | High | 9.17 | 0.544 | 5.9% | 0.107 | 1.2% | 0.532 | 5.8% | 0.768 | 8.4% |
| LYM# | Low | 0.97 | 0.094 | 9.6% | 0.000 | 0.0% | 0.070 | 7.2% | 0.117 | 12.0% |
| LYM# | Normal | 3.34 | 0.211 | 6.3% | 0.098 | 2.9% | 0.232 | 7.0% | 0.329 | 9.8% |
| LYM# | High | 9.02 | 0.640 | 7.1% | 0.150 | 1.7% | 0.737 | 8.2% | 0.987 | 10.9% |
| MON# | Low | 0.25 | 0.040 | 15.6% | 0.012 | 4.7% | 0.000 | 0.0% | 0.042 | 16.3% |
| Parameter | Level | Mean | Within-Day | | Between-Day | | Between-Site | | Overall Reproducibility | |
| | | | SD | CV% | SD | CV% | SD | CV% | SD | CV% |
| MON# | Normal | 0.86 | 0.078 | 9.1% | 0.000 | 0.0% | 0.013 | 1.5% | 0.079 | 9.2% |
| MON# | High | 1.66 | 0.126 | 7.6% | 0.000 | 0.0% | 0.025 | 1.5% | 0.129 | 7.8% |
| EOS# | Low | 0.10 | 0.020 | 21.2% | 0.000 | 0.0% | 0.000 | 0.0% | 0.020 | 21.2% |
| EOS# | Normal | 0.30 | 0.041 | 13.7% | 0.000 | 0.0% | 0.007 | 2.4% | 0.042 | 13.9% |
| EOS# | High | 0.69 | 0.059 | 8.5% | 0.000 | 0.0% | 0.012 | 1.8% | 0.060 | 8.7% |
| BAS# | Low | 0.01 | 0.002 | NA | 0.000 | NA | 0.001 | NA | 0.002 | NA |
| BAS# | Normal | 0.04 | 0.004 | NA | 0.000 | NA | 0.002 | NA | 0.004 | NA |
| BAS# | High | 0.09 | 0.005 | NA | 0.001 | NA | 0.002 | NA | 0.006 | NA |
| NEU% | Low | 52.57 | 2.002 | 3.8% | 0.000 | 0.0% | 0.419 | 0.8% | 2.046 | 3.9% |
| NEU% | Normal | 49.49 | 1.340 | 2.7% | 0.443 | 0.9% | 1.388 | 2.8% | 1.979 | 4.0% |
| NEU% | High | 44.48 | 2.313 | 5.2% | 0.240 | 0.5% | 2.893 | 6.5% | 3.712 | 8.3% |
| LYM% | Low | 34.55 | 2.022 | 5.9% | 0.357 | 1.0% | 1.000 | 2.9% | 2.284 | 6.6% |
| LYM% | Normal | 37.16 | 1.237 | 3.3% | 0.641 | 1.7% | 1.584 | 4.3% | 2.109 | 5.7% |
| LYM% | High | 43.73 | 2.421 | 5.5% | 0.383 | 0.9% | 3.017 | 6.9% | 3.888 | 8.9% |
| MON% | Low | 9.04 | 1.276 | 14.1% | 0.383 | 4.2% | 0.259 | 2.9% | 1.357 | 15.0% |
| MON% | Normal | 9.56 | 0.777 | 8.1% | 0.120 | 1.3% | 0.273 | 2.9% | 0.832 | 8.7% |
| MON% | High | 8.05 | 0.458 | 5.7% | 0.000 | 0.0% | 0.102 | 1.3% | 0.469 | 5.8% |
| EOS% | Low | 3.42 | 0.698 | 20.4% | 0.000 | 0.0% | 0.025 | 0.7% | 0.699 | 20.4% |
| EOS% | Normal | 3.37 | 0.438 | 13.0% | 0.000 | 0.0% | 0.000 | 0.0% | 0.438 | 13.0% |
| EOS% | High | 3.33 | 0.249 | 7.5% | 0.000 | 0.0% | 0.120 | 3.6% | 0.276 | 8.3% |
| BAS% | Low | 0.42 | 0.052 | NA | 0.011 | NA | 0.000 | NA | 0.053 | NA |
| BAS% | Normal | 0.42 | 0.038 | NA | 0.000 | NA | 0.005 | NA | 0.039 | NA |
| BAS% | High | 0.41 | 0.021 | NA | 0.000 | NA | 0.001 | NA | 0.021 | NA |

Reproducibility for the Combined Sites

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13

Interference- (CLSI EP7-A2 and CLSI H26-A2)

To evaluate potential interferences, high levels of bilirubin (conjugated), triglycerides, WBCs, PLT and NRBCs were tested by the HemoScreen system according to CLSI EP07-A2.

Blood samples were acquired as follows:

Lipemia- 11 blood sample remnants with triglyceride concentration greater than 300 mg/dL. ●
Bilirubin- 3 blood samples with initial total blood volume of more than 3 mL were manipulated . with exogenous bilirubin to target the desired bilirubin levels.
. Leukocytosis, thrombocytosis, and NRBC flagged samples were chosen according to established criteria. The sample set included nine blood samples with high WBC levels (>50x103/uL), eight blood samples with high PLT levels (>700x102/uL), and nine samples which flagged NRBC by the laboratory reference method.

For lipemia, all measurands were analyzed. For bilirubin, the following 10 measurands were analyzed: WBC, RBC, HGB, HCT, MCV, MCH, MCHC, RDW, PLT and MPV. For leukocytosis, RBC, HGB, MCV and PLT were analyzed. For thrombocytosis, WBC, RBC, HGB, PLT and MPV were analyzed. For NRBC flagged samples, WBC and the differentials were analyzed.

For all evaluations except bilirubin, samples were tested in duplicate or triplicate by HemoScreen and by a reference device (in singleton or in duplicate) that reports no interference from these substances (control group results). The averaged HemoScreen results were compared to the average of duplicate results (or the single result) from the control group and analyzed by paired difference testing. For bilirubin, only HemoScreen testing was performed, where the "spiked results" were compared to results from testing with neat samples (no exogenous bilirubin added). Again, the results were analyzed by paired difference testing.

There was no significant bilirubin interference up to a concentration 50 mg/dL for the following parameters: WBC, HGB, RBC, HCT, MCV, MCH, MCHC, and RDW. There was no significant bilirubin interference up to a concentration of 30 mg/dL for PLT and MPV. No interference was identified from high triglyceride levels (319-729 mg/dL), and no interference was noted from high levels of WBC (up to 317x103/uL), PLT (up to 2,045x103/uL), or NRBCs.

Whole Blood Stability

Eighteen (18) freshly collected venous whole blood samples were collected from volunteer subjects. The venous blood samples were collected into K2EDTA tubes. Efforts were made to collect samples that spanned as wide a range as possible for the WBC, RBC, HGB, HCT, and PLT parameters.

Each blood sample was measured in duplicate with results averaged to obtain the baseline at time zero (T0). The samples were subsequently kept at RT (22°-25°C) and were analyzed again, in duplicate (with results averaged), at the following time points: 2 hours, 6 hours, 7 hours and 8 hours. The ratio of T(x) to T0 was calculated and averaged for all blood samples for each parameter and each time point.

The results confirmed that performance at all time points, and for all parameters, met the acceptance criteria. Therefore, the data validated that venous blood samples stored at room

14

temperature can be analyzed on the HemoScreen for seven (7) hours from the time of blood collection without compromising the performance characteristics.

807.92 (b)(2): Brief Description of Clinical Data

Method Comparison & Clinical Sensitivity/Specificity

The objective of the study was to evaluate the comparability and clinical sensitivity of the HemoScreen analyzer. A total of 495 normal and pathological residual whole blood specimens were collected across three clinical sites. Different HemoScreen devices and cartridge/sampler batches were used by several operators at each site. Each of the samples was analyzed twice on the HemoScreen (first usable replicate result used for data analyses) by operators who resembled the intended users in terms of education and experience, and twice on the predicate by laboratory personnel (the comparative results were averaged for data analyses). Three blood film slides were prepared for each sample for measurement by an automated blood smear (differential) method (2 slides/200 cells counted per slide for a total of 400 cell differential according to CLSI H20-A2). Experienced operators trained to use the automated blood smear performed the differentials, including morphology evaluation, and the results were verified by these operators.

15

| Parameter | Comparator | Pearson Correlation
Coefficient (r) | Intercept | Lower
95% CL | Upper
95% CL | Slope | Lower
95% CL | Upper
95% CL | Mean Bias | Mean Relative Bias |
|-----------------|-------------|----------------------------------------|-----------|-----------------|-----------------|-------|-----------------|-----------------|-----------|--------------------|
| WBC (x 103/μL) | Sysmex | 0.993 | -0.256 | -0.396 | -0.116 | 1.040 | 1.019 | 1.061 | 0.09 | -0.14% |
| RBC (x 106/μL) | Sysmex | 0.989 | 0.021 | -0.047 | 0.088 | 1.000 | 0.983 | 1.016 | 0.02 | 0.52% |
| HGB (g/dL) | Sysmex | 0.985 | -0.334 | -0.549 | -0.119 | 1.038 | 1.019 | 1.056 | 0.13 | 0.81% |
| HCT (%) | Sysmex | 0.982 | -0.184 | -0.872 | 0.505 | 1.036 | 1.017 | 1.056 | 1.15 | 3.05% |
| MCV (fL) | Sysmex | 0.956 | -2.367 | -6.216 | 1.482 | 1.053 | 1.009 | 1.096 | 2.27 | 2.53% |
| MCH (pg) | Sysmex | 0.957 | 0.131 | -0.560 | 0.822 | 0.998 | 0.974 | 1.021 | 0.06 | 0.20% |
| MCHC (g/dL) | Sysmex | 0.675 | 8.309 | 5.921 | 10.697 | 0.727 | 0.655 | 0.799 | -0.78 | -2.34% |
| RDW (%) | Sysmex | 0.946 | 0.504 | -0.018 | 1.025 | 0.965 | 0.928 | 1.002 | -0.03 | -0.12% |
| PLT (x 103/μL) | Sysmex | 0.967 | -6.581 | -10.494 | -2.668 | 1.093 | 1.068 | 1.118 | 14.57 | 5.12% |
| MPV (fL) | Sysmex | 0.831 | 0.043 | -0.660 | 0.745 | 1.016 | 0.949 | 1.082 | 0.21 | 1.93% |
| NEU (x 103/μL) | Sysmex | 0.989 | 0.026 | -0.069 | 0.120 | 1.032 | 1.007 | 1.057 | 0.22 | 3.83% |
| LYM (x 103/μL) | Sysmex | 0.997 | -0.003 | -0.037 | 0.032 | 1.058 | 1.035 | 1.082 | 0.12 | 5.46% |
| MON (x 103/μL) | Sysmex | 0.718 | -0.014 | -0.077 | 0.049 | 0.781 | 0.671 | 0.892 | -0.16 | -27.08% |
| EOS (x 103/μL) | Sysmex | 0.981 | -0.002 | -0.007 | 0.003 | 0.984 | 0.915 | 1.053 | -0.00 | -4.33% |
| BAS (x 103/μL)* | Sysmex | NA | NA | NA | NA | NA | NA | NA | NA | NA |
| NEU (%) | Sysmex | 0.984 | 2.161 | 1.182 | 3.139 | 0.996 | 0.978 | 1.014 | 1.90 | 3.71% |
| NEU (%) | Blood Smear | 0.960 | -0.125 | -2.045 | 1.795 | 1.000 | 0.967 | 1.033 | -0.30 | -0.23% |
| LYM (%) | Sysmex | 0.991 | 0.411 | -0.011 | 0.833 | 1.029 | 1.007 | 1.051 | 0.96 | 5.11% |
| LYM (%) | Blood Smear | 0.961 | 1.173 | 0.806 | 1.541 | 1.016 | 0.988 | 1.045 | 1.01 | 8.45% |
| MON (%) | Sysmex | 0.780 | -0.370 | -1.271 | 0.531 | 0.809 | 0.693 | 0.924 | -1.87 | -26.90% |
| MON (%) | Blood Smear | 0.594 | 0.159 | -0.316 | 0.634 | 0.944 | 0.851 | 1.038 | -0.17 | -2.41% |
| EOS (%) | Sysmex | 0.981 | 0.005 | -0.002 | 0.013 | 0.949 | 0.893 | 1.006 | -0.06 | -2.97% |
| EOS (%) | Blood Smear | 0.943 | 0.009 | -0.031 | 0.049 | 1.170 | 1.045 | 1.296 | 0.13 | 16.01% |
| BAS (%)* | Sysmex | NA | NA | NA | NA | NA | NA | NA | NA | NA |
| BAS (%)* | Blood Smear | NA | NA | NA | NA | NA | NA | NA | NA | NA |

Correlation and Bias of HemoScreen Compared to Standard Method and Blood Smears – Combined Sites (excluding flagged parameters)

For all parameters, for both comparators, and for all values with or without flagged results, the 95% confidence intervals for mean bias / mean relative bias were within the acceptance limits.

For MON# and MON%, the point estimate of the correlation between the Sysmex met the acceptance limit when

16

flagged results were excluded. For the rest of parameters, and for all results, with and without flags, the correlation point estimates met the acceptance criteria.

*NOTE: Basophil data are not provided in the previous table, as the distribution of samples with low-to-high was not achieved and the data were not meaningful. Therefore, in a separate study that focused on basophils only, 95 whole blood samples that included high levels of basophils were analyzed by HemoScreen and by light microscopy. The table below describes of various basophil levels in each study.

		BAS>1%	BAS>2%	BAS>3%	BAS>4%
Clinical studies
N = 495	Blood smear	15.73%	3.73%	1.04%	0.21%
BASO study
N = 95	Blood smear	31.52%	15.22%	6.52%	3.26%

The data from the "BASO Study" were analyzed using light microscopy (the standard reference method) to determine %basophils, and the Sysmex method to determine absolute counts. This dual process was required as the blood smear method does not provide counts. The data are as follows:

| Parameter | Comparator | Pearson Correlation
Coefficient (r) | Intercept | Lower
95% CL | Upper 95%
CL | Slope | Lower
95% CL | Upper 95%
CL | Mean Bias | Mean Relative Bias |
|----------------|-------------|----------------------------------------|-----------|-----------------|-----------------|-------|-----------------|-----------------|-----------|--------------------|
| BAS (x 10³/μL) | Sysmex | 0.484 | 0.007 | -0.008 | 0.023 | 0.866 | 0.333 | 1.398 | 0.04 | 11.87% |
| BAS (%) | Blood Smear | 0.725 | 0.334 | 0.260 | 0.408 | 0.466 | 0.209 | 0.724 | -0.01 | 43.99% |

Correlation and Bias of HemoScreen Compared to Standard Method and Blood Smears (Basophils)

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Flagging

The WBC flagging rate for HemoScreen was compared to the WBC differential results displayed by the predicate and blood smears for the same samples. Two types of abnormalities were evaluated: (1) distributional abnormal samples, which are samples where the quantity of at least one of the differential parameters resides outside of the normal concentrations, and (2) morphological abnormal samples, which are samples that contain atypical forms of the normal cell types contained in ordinary blood samples. A total of 402 whole blood specimens were analyzed across three clinical sites. The ability to identify abnormal samples and listed pathologies was evaluated according to CLSI H20-A2 by creating predictive value tables for distributional and morphological classifications, separately and combined. From these tables, the positive percent agreement (PPA), negative percent agreement (NPA), and overall agreement were calculated along with their respective exact binomial 95% two-sided confidence intervals across the three sites. All these analyses were performed for each abnormality type (distributional and morphological) separately and for the overall sensitivity to abnormal WBC.

| | % | Lower
95% CL | Upper
95% CL |
|-------------------|-------|-----------------|-----------------|
| PPA | 95.9% | 93.0% | 97.9% |
| NPA | 82.1% | 73.4% | 88.8% |
| Overall Agreement | 92.3% | 89.2% | 94.7% |

Diagnostic Accuracy - Overall WBC Flagging, HemoScreen versus Predicate

		Diagnostic Accuracy - Overall WBC Flagging, HemoScreen versus Blood Smear

| | % | Lower
95% CL | Upper
95% CL |
|-------------------|-------|-----------------|-----------------|
| PPA | 93.8% | 90.3% | 96.3% |
| NPA | 71.7% | 62.4% | 79.8% |
| Overall Agreement | 87.6% | 83.9% | 90.6% |

Reference Intervals- Adult Males and Females (CLSI EP28-A3C)

The reference intervals study was conducted at a single US site. The target was to evaluate a minimum of 120 male subjects and 120 female subjects. One tube of freshly collected K2EDTA venous blood was collected from healthy (self-reported) adult (19-69 years old) male and female volunteers on a single occasion. Each blood sample was analyzed by HemoScreen by routine

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procedure in one replicate, and all 20 parameters were reported. The reference intervals were calculated in accordance with CLSI standard EP28-A3C; namely, 95% distribution-freereference intervals (male and female) were identified per parameter, which were based on the 2.5th and 97.5th percentiles of each variable. The results are presented below.

Parameter	Female (n=123)		Male (n=120)
	Lower Limit	Upper Limit	Lower Limit	Upper Limit
WBC (x 103/μL)	4.0	11.5	3.6	10.2
RBC (x 106/μL)	3.6	5.1	4.2	6.0
HGB (g/dL)	10.8	15.6	12.5	17.6
HCT (%)	32.9	45.6	39.0	52.0
MCV (fL)	78.1	99.2	74.9	98.0
MCH (pg)	24.4	32.8	23.8	32.8
MCHC (g/dL)	30.7	34.7	30.9	35.6
RDW (%)	11.7	16.1	11.8	14.9
PLT (x 103/μL)	179	450	141	437
MPV (fL)	9.6	14.0	9.3	15.9
NEUT (x 103/μL)	1.8	8.4	1.7	7.4
LYMP (x 103/μL)	1.3	3.9	1.2	3.8
MONO (x 103/μL)	0.1	0.6	0.1	0.8
EOS (x 103/μL)	0.0	0.4	0.0	0.5
BASO (x 103/μL)	0.00	0.03	0.00	0.02
NEUT (%)	41.0	79.6	34.7	73.4
LYMP (%)	16.7	51.7	20.7	56.9
MONO (%)	1.7	7.5	1.7	9.4
EOS (%)	0.3	5.9	0.3	7.7
BASO (%)	0.0	0.3	0.0	0.4

HemoScreen Reference Intervals for All Parameters

Vein to Capillary Equivalency

The objective of the study was to demonstrate equivalency between capillary K2EDTA whole blood samples and venous K2EDTA whole blood samples using the HemoScreen device. A total of 75 normal and pathological paired capillary and venous whole blood specimens were drawn from volunteer subjects across three clinical sites. Each of the venous and capillary specimens was assayed once on the HemoScreen by the intended users, twice on the predicate by laboratory personnel, and samples were also measured by an automated blood smear method (2 slides/200 cells counted per slide for a total of 400 cells) by experienced operators who also verified its results.

The capillary whole blood results obtained from the HemoScreen were compared to the corresponding results from:

1. The venous whole blood results of the same donor obtained from the HemoScreen.
1. The capillary whole blood results of the same donor obtained from the comparative method.

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For all 20 parameters, against all comparators, for all values with and without flagged results, the 95% confidence intervals for mean bias / mean relative bias were within the acceptance limits.

For MON%, the point estimate of the correlation between capillary and blood smear capillary met the acceptance limit when flagged results were excluded. For the rest of parameters, against all comparators, and for all results with and without flags, the correlation point estimates met the acceptance criteria.

The results demonstrated comparable performance characteristics for capillary and venous whole blood specimens, and therefore support the claim of using the two specimen types for measurement on the HemoScreen.

807.92 (b)(3): Conclusions from Nonclinical and Clinical Data

The conclusions drawn from the analytical and clinical data demonstrate that the device is safe and effective for its intended use.