The Navios EX Flow Cytometer is intended for use as an in vitro diagnostic device for immunophenotyping using up to four fluorescent detection channels using a blue (488 nm) laser and two light scatter detection channels. It is intended for use with in vitro diagnostic (IVD) assays and software that are indicated for use with the instrument.

The Navios EX tetra Software is intended for use as an in vitro diagnostic device for immunophenotyping with CYTO-STAT tetraCHROME CD45-FITC/CD4-RD1/ CD8-ECD/CD3-PC5 and CYTO-STAT tetraCHROME CD45-FITC/CD56-RD1/CD19-ECD/CD3-PC5 monoclonal antibody reagents on the Navios EX Flow Cytometer.

It provides automated analysis and results for the identification and enumeration of CD3+CD4+, CD3+CD8+, CD3+, CD19+ and CD3-CD56+ lymphocyte percentages and absolute counts in peripheral whole blood. Absolute counts may be determined by the Navios EX Flow Cytometers using Flow-Count Fluorospheres (Single Platform Technology (SPT) Method) or separate hematology results (Dual Platform Method). It is indicated for use in the immunologic assessment of patients having or suspected of having immune deficiency.

Device Description

The Navios EX Flow Cytometry System consists of:

Navios EX Flow Cytometer
Navios EX tetra Software
Navios EX Software off-line analysis tool
CYTO-STAT tetraCHROME reagents
Flow-Set Pro Fluorospheres
Flow-Check Pro Fluorospheres
Flow-Count Fluorospheres
Immuno-Trol Cells
Immuno-Trol Low Cells
COULTER IMMUNOPREP Reagent System
QuickCOMP 2 and QuickCOMP 4 Kits
CYTO-COMP Cell Kit
ISOFLOW Sheath Fluid
FlowClean Cleaning Reagent
TQ-Prep Workstation (accessory for sample preparation)
PrepPlus 2 Workstation (accessory for sample preparation)

The Navios EX Flow Cytometry System is the next generation product in the Navios Flow Cytometry family. With the Navios EX flow cytometer and associated software, the following modifications have been introduced:

Replacement of optical assemblies and flow cell
Replacement of the existing 488nm laser with a comparable 488nm laser
Replacement of the band-pass filter (FL3) used for ECD dye
Replacement of the Forward Scatter mask with a new mask configuration
Replacement of the existing fixed aspiration probe with an adjustable one. This probe is adjusted by the service engineer only to account for the sample tube employed at the customer's laboratory.
Change to the optics module temperature management hardware
Minor change to the sheath pressure
Minor changes to the Navios EX tetra algorithm

AI/ML Overview

Here's a breakdown of the acceptance criteria and study information for the Navios EX Flow Cytometry System, based on the provided FDA 510(k) summary:

1. Table of Acceptance Criteria and Reported Device Performance

Study/Performance Characteristic	Acceptance Criteria (Implied by study goal)*	Reported Device Performance
Laser Performance Characteristics	Verify stability of laser performance over time.	Stable over time.
Instrument Carryover	Meet performance specifications for carryover.	Meets carryover performance requirements.
Instrument Linearity	Demonstrate linear fluorescence detection.	Linearity of fluorescence measurements was demonstrated.
Assay Carryover	Meet performance specifications for carryover of whole blood and reagents.	Meets carryover performance requirements.
Assay Linearity	Verify the linear range of absolute values for each lymphocyte subset.	Meets linearity performance requirements.
Detection Capability	Meet performance requirements for Limit of Blank (LoB), Limit of Detection (LoD), Limit of Quantitation (LLoQ).	Meets LoB, LoD, and LLoQ requirements in whole blood.
Specimen and Prepared Sample Stability	Verify specimen and prepared sample stability claims (24 hours room temp for specimen, 2 hours room temp/24 hours refrigerated for prepared sample).	Meets requirements for specimen and prepared sample stability.
Analytical Measuring Interval (AMI)	AMI verified to meet acceptance criteria.	AMI was verified to meet acceptance criteria.
Comparability of Navios EX Models (6C/2L, 8C/2L, 10C/3L)	Verify comparability of performance of each Navios EX configuration to the predicate Navios.	Meets performance requirements when compared to the predicate device.
Precision – Across Model Configurations	Demonstrate system imprecision using control material.	Meets performance requirements.
Method Comparison	Evaluate bias between the subject device versus the predicate.	Meets performance requirements when compared to the predicate device.
Precision — Long Term Imprecision	Demonstrate system imprecision using control material over long term.	Meets performance requirements for Long Term Imprecision.
Precision — Whole Blood Repeatability	Evaluate sample imprecision at various medical decision levels.	Meets performance requirements for Whole Blood Repeatability.
Precision — Whole Blood Repeatability – Site To Site Variability	Evaluate site-to-site variability for CD3+CD4+ percentage and absolute counts.	Site-to-site variability for CD3+CD4+ percentages and absolute counts were found to be acceptable.
Adult Reference Interval	Establish and confirm consistency with published values for T, B, and NK lymphocyte subsets.	Established and confirmed to be consistent with published values.

Note: The document generally states "meets performance requirements" rather than explicit numerical acceptance criteria. The implied acceptance criteria are that the device performs within acceptable limits for the given test, as outlined by the testing approach and referenced standards/guidance.

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

The document does not explicitly state the numerical sample size for the test set for each individual study. It broadly refers to "data collected" and "analysis of the data collected."

However, it does indicate that whole blood samples were used for several studies (e.g., Assay Carryover, Detection Capability, Whole Blood Repeatability, Site-to-Site Variability).

Data Provenance: Not explicitly stated (e.g., country of origin). The studies appear to be internal validation studies conducted by the manufacturer, Beckman Coulter Inc., based in Miami, FL. There is no indication of retrospective or prospective data collection for the test sets.

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

This information is not provided in the document. The studies listed are primarily focused on the analytical performance of the flow cytometer and software, not on subjective interpretations requiring expert consensus for ground truth.

4. Adjudication Method for the Test Set

This information is not applicable and not provided. As the studies are focused on the analytical performance and comparison to a predicate device, there is no mention of adjudication methods typically associated with human interpretation or subjective assessments.

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

No, a Multi-Reader Multi-Case (MRMC) comparative effectiveness study was not done. This type of study typically evaluates diagnostic accuracy with human readers, with and without AI assistance. The Navios EX Flow Cytometry System is an automated laboratory device, and its validation focuses on analytical performance and equivalence to a predicate device, rather than human interpretation aided by AI.

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

Yes, a standalone performance evaluation was done. The studies listed (e.g., Laser Performance, Instrument Carryover, Linearity, Detection Capability, Precision, Method Comparison) directly assess the performance of the Navios EX Flow Cytometry System (instrument and software) without human intervention in the result generation process. The device's "automated analysis and results" indication for the Navios EX tetra Software also implies standalone capability.

7. Type of Ground Truth Used

The ground truth for most studies appears to be based on:

Established analytical methodologies: Performance is evaluated against known physical properties (e.g., linearity of fluorescence, stability of laser), or against established and validated methods (e.g., the predicate device for method comparison, or control materials for precision).
Performance specifications: The device is expected to meet certain predefined specifications (e.g., for carryover, detection limits).
Published values: For the "Adult Reference Interval" study, the established intervals were confirmed to be "consistent with published values."

There is no mention of "expert consensus," "pathology," or "outcomes data" being used as ground truth for these analytical performance studies.

8. Sample Size for the Training Set

This information is not provided in the document. The Navios EX system is an update to an existing device (Navios Flow Cytometer). While the Navios EX tetra Software has "minor modifications implemented to address differences in select data patterns seen on the Navios EX," it's unclear if these modifications involved a distinct "training set" in the machine learning sense, or if "training" refers more to software development and tuning against internal data. Given the context of a 510(k) for an automated lab instrument, it's more likely the latter, and explicit machine learning training set sizes are typically not detailed in such submissions unless the AI component is a central, novel feature requiring extensive independent validation.

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

This information is not provided in the document. As noted above, the concept of a "training set" and its associated ground truth establishment methods are not explicitly discussed in this 510(k) summary, likely because the primary validation focuses on the analytical performance and substantial equivalence of the instrument system, rather than a novel, data-driven AI algorithm requiring extensive training data. If software algorithm adjustments were made, the "ground truth" for those adjustments would likely derive from internal testing and expected performance based on the predicate device's behavior.

Summary

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Public Health Service

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

June 23, 2017

Beckman Coulter Zaily Rodriguez Staff Regulatory Affairs Specialist 11800 Sw 147th Ave Miami, Florida 33196-2500

Re: K162897

Trade/Device Name: Navios EX Flow Cytometer, 6 Color/2 Laser, Navios EX Flow Cytometer, 8 Color/2 Laser, Navios EX Flow Cytometer, 10 Color/3 Laser Regulation Number: 21 CFR 864.5220 Regulation Name: Automated differential cell counter Regulatory Class: Class II Product Code: OYE, PDX Dated: May 24, 2017 Received: May 25, 2017

Dear Zaily Rodriguez:

We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food. Drug. and Cosmetic Act (Act) that do not require approval of a premarket approval application (PMA). You may, therefore, market the device, subject to the general controls provisions of the Act. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.

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

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

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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); 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 and Part 809), 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/ResourcesforYou/Industry/default.htm. 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 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.

Kelly Oliner -S

For Leonthena R. Carrington, M.S., MBA, MT 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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510(k) Number (if known) K162897

Device Name Navios EX Flow Cytometer

Indications for Use (Describe)

The Navios EX Flow Cytometer is intended for use as an in vitro diagnostic device for immunophenotyping using up to four fluorescent detection channels using a blue (488 mm) laser and two light scatter detection channels. It is intended for use with in vitro diagnostic (IVD) assays and software that are indicated for use with the instrument.

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)

CONTINUE ON A SEPARATE PAGE IF NEEDED.

This section applies only to requirements of the Paperwork Reduction Act of 1995.

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

The burden time for this collection of information is estimated to average 79 hours per response, including the time to review instructions, search existing data sources, gather and maintain the data needed and complete and review the collection of information. Send comments regarding this burden estimate or any other aspect of this information collection, including suggestions for reducing this burden, to:

Department of Health and Human Services Food and Drug Administration Office of Chief Information Officer Paperwork Reduction Act (PRA) Staff PRAStaff@fda.hhs.gov

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Form Approved: OMB No. 0910-0120 Expiration Date: January 31, 2017 See PRA Statement below.

510(k) Number (if known) K162897

Device Name

CYTO-STAT tetraCHROME CD45-FITC/CD4-RD1/CD8-ECD/CD3-PC5 and CYTO-STAT tetraCHROME CD45-FITC/CD56-RD1/CD19-ECD/CD3-PC5 Monoclonal Antibody Reagents

Indications for Use (Describe)

CYTO-STAT tetraCHROME CD45-FITC/CD4-RD1/CD8-ECD/CD3-PC5 and CYTO-STAT tetraCHROME CD45-FITC/CD56-RD1/CD19-ECD/CD3-PC5 Monoclonal Antibody Reagents are for use on the COULTER EPICS XL/XL-MCL. Cytomics FC 500. Navios and Navios EX Flow Cytometers. The reagents are also used with the tetraONE System for COULTER EPICS XL/XL-MCL Flow Cytometer, the tetraCXP System for FC 500 Flow Cytometry System, Navios tetra Software for the Navios System, and Navios EX tetra Software for the Navios EX System.

Used alone or in combination with the automated systems, the reagents are intended "For In Vitro Diagnostic Use" and allow simultaneous identification and enumeration of total CD3+, total CD8+, dual CD3+CD4+, dual CD3+CD8+ and/or total CD3+, CD19+ and CD3-CD56+ lymphocyte percentages and absolute counts in whole blood by flow cytometry. The systems also provide the CD4/CD8 ratio when using CD45-FITC/CD4-RD1/CD8-ECD/ CD3-PC5. These reagents are indicated for use in the immunologic assessment of patients having or suspected of having immune deficiency.

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

X Prescription Use (Part 21 CFR 801 Subpart D)

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

CONTINUE ON A SEPARATE PAGE IF NEEDED.

This section applies only to requirements of the Paperwork Reduction Act of 1995.

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

Department of Health and Human Services Food and Drug Administration Office of Chief Information Officer Paperwork Reduction Act (PRA) Staff PRAStaff(@fda.hhs.gov

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510(k) Number (if known)

Device Name Flow-Set Pro Fluorospheres

Indications for Use (Describe)

Flow-Set Pro Fluorospheres is a suspension of fluorescent microspheres used as an aid in standardizing forward scatter, side scatter, and fluorescence detectors (FL1-4) on the Cytomics FC 500, Navios and Navios EX Flow Cytometers.

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)

CONTINUE ON A SEPARATE PAGE IF NEEDED.

This section applies only to requirements of the Paperwork Reduction Act of 1995.

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

Department of Health and Human Services Food and Drug Administration Office of Chief Information Officer Paperwork Reduction Act (PRA) Staff PRAStaff(@fda.hhs.gov

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510(k) Number (if known)

Device Name Flow-Count Fluorospheres

Indications for Use (Describe)

Flow-Count Fluorospheres is a fluorescent microsphere reagent for direct determination of lymphocyte subsets cell population percentages and absolute counts in biological specimens using EPICS XL/XL-MCL, Cytomics FC500, Navios and Navios EX flow cytometry systems as well as CD34+ cell population percentages and absolute counts in biological specimens using EPICS XL/XL-MCL and Cytomics FC500 flow cytometry systems.

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)

CONTINUE ON A SEPARATE PAGE IF NEEDED.

This section applies only to requirements of the Paperwork Reduction Act of 1995.

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

Department of Health and Human Services Food and Drug Administration Office of Chief Information Officer Paperwork Reduction Act (PRA) Staff PRAStaff(@fda.hhs.gov

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510(k) Summary for Navios EX Flow Cytometry System

510(k) Owner / Submitter Information

Name: Beckman Coulter Inc. Address: 11800 SW 147th Ave., Miami, FL 33196 Phone #: (305) 380-4191 Contact Person: Nancy Nadler Email Address: nancy.nadler@beckman.com Date Submitted: 24 May 2017

Device Information

Trade Name: Navios EX Flow Cytometer Classification: Class II Classification Name: Automated Differential Cell Counter (21 CFR 864.5220) Product Code: OYE Panel: Hematology Original 510(k) Clearance / Predicate: K130373, SE date: September 18, 2013

Trade Name: Navios EX tetra Software Classification: Class II Classification Name: Automated Differential Cell Counter (21 CFR 864.5220) Product Code: OYE Panel: Hematology Original 510(k) Clearance / Predicate: K130373, SE date: September 18, 2013

Predicate Device Information

Predicate Product	510(k)Number	DateCleared	Classification	21 CFR	ProductCode
Navios Flow Cytometer	K130373	9/18/13	Class II	864.5220	OYE
Navios tetra Software	K130373	9/18/13	Class II	864.5220	OYE

Device Description

The Navios EX Flow Cytometry System consists of:

Navios EX Flow Cytometer
Navios EX tetra Software
Navios EX Software off-line analysis tool
CYTO-STAT tetraCHROME reagents

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Flow-Set Pro Fluorospheres ●
. Flow-Check Pro Fluorospheres
Flow-Count Fluorospheres
. Immuno-Trol Cells
Immuno-Trol Low Cells
. COULTER IMMUNOPREP Reagent System
. QuickCOMP 2 and QuickCOMP 4 Kits
CYTO-COMP Cell Kit
ISOFLOW Sheath Fluid
FlowClean Cleaning Reagent
TQ-Prep Workstation (accessory for sample preparation) ●
. PrepPlus 2 Workstation (accessory for sample preparation)

Technological Characteristics Comparison to Predicate (Refer to Tables 1 and 2)

Replacement of optical assemblies and flow cell
. Replacement of the existing 488nm laser with a comparable 488nm laser
. Replacement of the band-pass filter (FL3) used for ECD dye
Replacement of the Forward Scatter mask with a new mask configuration
. Replacement of the existing fixed aspiration probe with an adjustable one. This probe is adjusted by the service engineer only to account for the sample tube employed at the customer's laboratory.
. Change to the optics module temperature management hardware
Minor change to the sheath pressure ●
Minor changes to the Navios EX tetra algorithm

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Table 1: Similarities between Navios and Navios EX Flow Cytometers

Attribute	Navios Flow Cytometer(Predicate)K130373	New Navios EX Flow Cytometer(Subject Device)
Intended Use	The Navios Flow Cytometer is intended for use as an in vitrodiagnostic device for immunophenotyping. It can be used inconjunction with the following monoclonal antibody reagentsand software package:CYTO-STAT tetraCHROME CD45-FITC/CD4-RD1/CD8-ECD/CD3-PC5 and CYTO-STAT tetraCHROME CD45-FITC/CD56-RD1/CD19-ECD/CD3-PC5 monoclonal antibodyreagents. These reagents provide identification andenumeration of CD3+CD4+, CD3+CD8+, CD3+, CD19+ andCD3-CD56+ lymphocyte percentages and absolute countsin peripheral whole blood. Absolute counts may bedetermined by the Navios flow cytometer using Flow-CountFluorospheres (single platform technology method) orseparate hematology results (dual platform method). Thesereagents are indicated for use in the immunologicassessment of patients having or suspected of havingimmune deficiency. Navios tetra Software for automated analysis and resultswith CYTO-STAT tetraCHROME CD45-FITC/CD4-RD1/CD8-ECD/CD3-PC5 and CYTO-STAT tetraCHROME CD45-FITC/CD56-RD1/CD19-ECD/CD3-PC5 monoclonal antibodyreagents.Navios Software may be installed on an independent computerworkstation for off-line analysis of listmode files generated by theNavios Flow Cytometer with the monoclonal antibody reagentsand software package listed above. The off-line analysis must beperformed in accordance with the product labeling.	Similar – Differences are underlined:The Navios EX Flow Cytometer is intended for use as an in vitrodiagnostic device for immunophenotyping using up to fourfluorescent detection channels with a blue (488 nm) laser andtwo light scatter detection channels. It is intended for usewith in vitro diagnostic (IVD) assays and software that areindicated for use with the instrument.
Device Classification	864.5220, Automated Differential Cell Counter	Same
Attribute	Navios Flow Cytometer(Predicate)K130373	New Navios EX Flow Cytometer(Subject Device)
Product Code	OYE	Same
Manufacturer	Beckman Coulter, Inc.	Same
Safety Features	Interlocks and mitigation of hazards via software and hardware controls	Same
SoftwareArchitecture	The acquisition software enables the user to acquire data from the instrument and to analyze, display, print and export acquired listmode data. The embedded software resides in the instrument. It controls the instrument functionality including the multi-carousel loader (MCL) for sample introduction.	Same
	The embedded software controls the instruments' lasers, acquisition system and fluidics. The instrument fluidics aspirates the sample, and performs instrument maintenance functions such as startup/shutdown. The embedded software also captures and provides the data to the workstation for processing.
	Pre-Analytic Features
	System Configuration	• Bench top• Printer• PC based workstation running Microsoft Windows Vista or WIN7 application specific software
		• Two tube monoclonal antibody reagent assay◦ CD45-FITC/CD4-RD1/CD8-ECD/CD3-PC5◦ CD45-FITC/CD56-RD1/CD19-ECD/CD3-PC5• Provides identification and enumeration of Total CD3+, CD3+CD4+, CD3+CD8+, CD3-CD56+, and CD19+ percentages and absolute count results
	tetraCHROMEReagent Assay
tetraCHROMEReagents specimenand prepared samplestability claims	• Specimen stability - 24 hours room temperature• Prepared sample stability◦ 2 hours room temperature◦ 24 hours refrigerated temperature	Same
	Sample Preparationwith MonoclonalAntibodies	Off-board sample preparation following instructions provided with cleared monoclonal antibody reagent
Attribute	Navios Flow Cytometer(Predicate)K130373	New Navios EX Flow Cytometer(Subject Device)
Sample Presentation	Prepared sample added to a daughter tube	Same
Resuspension ofprepared sampleprior to introductionto system	Prepared sample is vortex mixed	Same
Sample Introduction	Tube sampler• Automated presentation with Multi-tube Carousel Loader(MCL) from 32 test tube capacity carousel• Manual presentation into a tube location on a MCL via tube access door	Same
Aspiration Pathway	Same aspiration pathway used for automated and manual presentation	Same
Sample Identification	Bar-code reading of carousel position and labeled sample tube.User may also identify samples based on carousel location with a worklist.	Same
Analytical Features
Maximum ParameterDetectors	Six (FS, SS, FL1 - FL4)	Same
Electronics	40 MHz samplingDigital integrator circuitry w/ early stage ADC	Same
Photomultipler Tubes(PMTs) / Colors	Standard 4 PMTs (FL1 - FL4) off of 488 nm laser	Same
Color Separation	Collimated beam is separated into desired components withdichroic filters.	Same
On-board analysissoftware	System Software available	Same with minor modifications made to accommodate the newlaser
Off-line analysissoftware	Off-line Software package available	Same with minor modifications made to accommodate the newlaser
Analysis Algorithm	Tetra analysis software available	Same with minor modifications implemented to addressdifferences in select data patterns seen on the Navios EX
Post-Analytical Features
Data Reporting	FlowPAGE, Panel Report, Plots and Statistics printouts	Same
Attribute	Navios Flow Cytometer(Predicate)K130373	New Navios EX Flow Cytometer(Subject Device)
Cleaning CycleBetween Samples	Executed with IsoFlow Sheath Fluid ensuring carryoverspecification is met	Same
Quality ControlTechniques	• Daily Instrument Checks• Commercial Controls• Inter-laboratory Quality Assurance Program (IQAP)	Same
Cleanse Cycle	Cleaning cycle performed with FlowClean cleaning reagent aspart of the daily shutdown process, before and after runningsamples with vital dyes that stain the tubing, and as part oftroubleshooting.	Same
Compensation and Sample Preparation Reagents
Reagents used forcompensation andsample preparation	CYTO-COMP Cell KitIMMUNOPREP Reagent SystemQuickCOMP2 and 4 KitsCytoTrol Cells	Same with the exception of not using CytoTrol
Controls and Calibrators
Assay Controls andCalibrators	Flow-Check Pro FluorospheresFlow-Count FluorospheresFlow-Set Pro FluorospheresIMMUNO-TROL CellsIMMUNO-TROL Low Cells	Same
Attribute	Navios Flow Cytometer(Predicate)K130373	New Navios EX Flow Cytometer(Subject Device)
Pre-Analytic Features
Sample AspirationProbe	Fixed height	Adjustable (by Beckman Coulter field service personnel)
Analytical Features
Lasers / DriverBoards	IVD configuration - 488 nm• Diode Pumped Solid State (DPSS), 22mW• 3 laser driver boards (488 nm, 638 nm, 405 nm)	IVD configuration - 488 nm: Same with the exception of:• Laser Diode, 55mW• Single custom laser driver board
Forward Angle LightScatter	• Forward scatter mask• Single lens collimates the light• Band-pass filter passes only 488nm light• Diode detector converts light into electrical signals	Same with the exception of the band-pass filter and forwardscatter mask redesign
Optics	Achromatic Crossed Cylinder Lens	Spherical and cylindrical lenses coupled to the flow cell
Flow Cell	• Channel Size: 140 x 460 microns• Sheath Flow Pressure: 4 psi• Thin wall to allow for gel coupling distance• Optics module temperature management hardware: twothermoelectric devices at the top and bottom of the opticsmodule box	New Flow Cell with modified channel size and sheath flowpressure. No gel coupling of the lens and optics moduletemperature management hardware modified.
Fluorescencecollection	Collection lens and light path• 1st and 2nd lens set:o Gel coupled to flow cell, numerical aperture (NA)=1.2o Light passes through optical fiber to PMT areao Light leaves the fiber and is collimatedo Collimated light is separated by filters into desired bandsPMTs detect light and convert to electrical signals	Collection lens and light path:• Spherical mirror and aspheric Schmidt lenso No gel coupling, NA=1.2.o Light passes through optical fiber to PMT areao Light leaves the fiber and is collimatedo Collimated light is separated by filters into desired bandsPMTs detect light and convert to electrical signals
Optical Filters	Optical Filters: (SP = Short Pass, BP = Band Pass)• FL1 FITC 550 SP - 525 BP• FL2 PE 595 SP - 575/30 BP• FL3 ECD 655 SP - 620/30 BP	All filters same with the exception of:FL3 ECD is 655 SP - 614/20 BP
Attribute	Navios Flow Cytometer(Predicate)K130373	New Navios EX Flow Cytometer(Subject Device)
	FL4 PC5 730 SP - 695/30 BP
Side Angle LightScatter	Separate lens system focuses the light onto an optical fiber Light exiting the optical fiber is focused onto a diode through a filter to pass 488nm only	Side Scatter light is collected from the same side of the flow cell and focused onto the optical fiber by the spherical mirror. The side scatter is split off from the fluorescence signal by a dichroic mirror before entering the filter/PMT assembly.
Gating Strategy	The main Lymphocyte population is determined through a gate including the LADJ and GADJ regions.	Minor changes to the algorithm to accommodate data pattern changes resulting from the new optics module.

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Table 2: Differences between Navios and Navios EX Flow Cytometers

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Intended Use:

Navios EX Flow Cytometry System Indications for Use:

The Navios EX Flow Cytometer is intended for use as an in vitro diagnostic device for immunophenotyping using up to four fluorescent detection channels using a blue (488 nm) laser and two light scatter detection channels. . It is intended for use with in vitro diagnostic (IVD) assays and software that are indicated for use with the instrument.

Navios EX tetra Software Indications for Use:

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Summary of Navios EX Flow Cytometer Performance Testing

Study	Testing Approach	FDA GuidanceDocuments	Standards/ References	Testing Results
LaserPerformanceCharacteristics	Verify stability of the laserperformance of the NaviosEX flow cytometer overtime.	None	None	Analysis of the data collecteddemonstrates that the Navios EXlaser performance is stable overtime.
InstrumentCarryover	To verify carryover usingFlow-Check Profluorospheres meetsperformance specifications.	Special Controls GuidanceDocument: PremarketNotifications forAutomated DifferentialCell Counters forImmature or AbnormalBlood Cells - Carryover(Section 12)	CLSI H26-A2; FDA StandardsRecognition #7-210	Analysis of the data collecteddemonstrates that the Navios EXmeets the carryover performancerequirements.
InstrumentLinearity	Verify fluorescencedetection is linear usingstandard Navios EX settings.	None	None	Linearity of fluorescencemeasurements wasdemonstrated.
AssayCarryover	To verify carryover of wholeblood and reagents on theNavios EX meetsperformance specifications.	Special Controls GuidanceDocument: PremarketNotifications forAutomated DifferentialCell Counters forImmature or AbnormalBlood Cells - Carryover(Section 12)	Validation, Verification, andQuality Assurance of AutomatedHematology Analyzers, ApprovedStandard - 2nd Edition; June2010; CLSI H26-A2; FDAStandards Recognition #7-210	Analysis of the data collecteddemonstrates that the Navios EXmeets carryover performancerequirements.
Study	Testing Approach	FDA GuidanceDocuments	Standards/ References	Testing Results
Assay Linearity	Verify the linear range of theabsolute values for eachlymphocyte subsetpopulations on the NaviosEX Flow Cytometry System.	Special Controls GuidanceDocument: PremarketNotifications forAutomated DifferentialCell Counters forImmature or AbnormalBlood Cells - Linearity(Section 11)	Evaluation of the Linearity ofQuantitative MeasurementProcedures: A StatisticalApproach; Approved Guideline;April 2003. CLSI EP06-A; FDAStandards Recognition #7-193	Analysis of the data collecteddemonstrates that the Navios EXmeets the linearity performancerequirements.
DetectionCapability	To verify that the Navios EXmeets the performancerequirements for Limit ofBlank (LoB), Limit ofDetection (LoD), Limit ofQuantitation (LLoQ).	None	Evaluation of DetectionCapability for Clinical LaboratoryMeasurement Procedures;Approved Guideline - SecondEdition; CLSI EP17-A2; FDAStandards Recognition #7-233	Analysis of the data collecteddemonstrates that the Navios EXmeets the performancerequirements for LOB, LOD, andLOQ in whole blood.
Specimen andPreparedSampleStability	Stability of whole bloodsamples will be evaluated toverify specimen andprepared sample stabilityclaims.	None	None	Analysis of the data collecteddemonstrates that the Navios EXFlow Cytometry System meets therequirements for specimen andprepared sample stability.

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Study	Testing Approach	FDA GuidanceDocuments	Standards/ References	Testing Results
AnalyticalMeasuringInterval	Establish the Navios EXAnalytical MeasuringInterval (AMI) based on thesystem's capability(Linearity, Limit ofQuantitation (LOQ)),consideration of thepredicate and theapplication's intended usepopulation.	None	None	AMI of the Navios EX was verifiedto meet the acceptance criteria.
Comparabilityof Navios EXModels(6C/2L, 8C/2L,10C/3L)	Verify comparability ofperformance of each NaviosEX configuration to thepredicate Navios.	Special Controls GuidanceDocument: PremarketNotifications forAutomated DifferentialCell Counters forImmature or AbnormalBlood Cells - Accuracy(Section 8)	Validation, Verification, andQuality Assurance of AutomatedHematology Analyzers, ApprovedStandard – 2nd Edition; June2010; CLSI H26-A2; FDAStandardsRecognition # 7-210CLSI EP09-A3, MethodComparison and Bias EstimationUsing Patient Samples; ApprovedGuideline--Second Edition(Interim Revision)	Analysis of the data collecteddemonstrates that the Navios EXFlow Cytometry System meets theperformance requirements whencompared to the predicate device.

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Study	Testing Approach	FDA GuidanceDocuments	Standards/ References	Testing Results
Precision –Across ModelConfigurations	Demonstrate systemimprecision using controlmaterial as a surrogate for astabilized sample on each ofthe three Navios EXconfigurations.	Special Controls GuidanceDocument: PremarketNotifications forAutomated DifferentialCell Counters forImmature or AbnormalBlood Cells - Precision(Section 9)	CLSI EP05-A2, Evaluation ofPrecision Performance ofQuantitative MeasurementMethods; Approved Guideline –Second Edition.	Analysis of the data collecteddemonstrates that the Navios EXmeets performance requirements.
MethodComparison	To evaluate bias betweenthe subject device versusthe predicate.	Special Controls GuidanceDocument: PremarketNotifications forAutomated DifferentialCell Counters forImmature or AbnormalBlood Cells - Accuracy(Section 8)	Validation, Verification, andQuality Assurance of AutomatedHematology Analyzers, ApprovedStandard – 2nd Edition; June2010; CLSI H26-A2; FDAStandardsRecognition # 7-210CLSI EP09-A3, MethodComparison and Bias EstimationUsing Patient Samples; ApprovedGuideline–Second Edition(Interim Revision)	Analysis of the data collecteddemonstrates that the Navios EXFlow Cytometry System meets theperformance requirements whencompared to the predicate device.
Study	Testing Approach	FDA GuidanceDocuments	Standards/ References	Testing Results
Precision —Long TermImprecision	Demonstrate systemimprecision using controlmaterial as a surrogate for astabilized sample	Special Controls GuidanceDocument: PremarketNotifications forAutomated DifferentialCell Counters forImmature or AbnormalBlood Cells - Precision(Section 9)	CLSI EP05-A2, Evaluation ofPrecision Performance ofQuantitative MeasurementMethods; Approved Guideline -Second Edition.	Analysis of the data collecteddemonstrates that the Navios EXmeets performance requirementsfor Long Term Imprecision.
Precision —Whole BloodRepeatability	Evaluate sample imprecisionusing a precision profileapproach to estimaterepeatability at variousmedical decision levels anddata percentiles.	Special Controls GuidanceDocument: PremarketNotifications forAutomated DifferentialCell Counters forImmature or AbnormalBlood Cells - Precision(Section 9)	CLSI H26-A2, Validation,Verification, and QualityAssurance of AutomatedHematology AnalyzersCLSI EP05-A2, Evaluation ofPrecision Performance ofQuantitative MeasurementMethods; Approved Guideline -Second Edition.	Analysis of the data collecteddemonstrates that the Navios EXmeets performance requirementsfor Whole Blood Repeatability.
Precision —Whole BloodRepeatability– Site To SiteVariability	Evaluate site-to-sitevariability performance ofCYTO-STAT tetraCHROMEreagents for CD3+CD4+percentage and absolutecounts using whole bloodspecimens	Special Controls GuidanceDocument: PremarketNotifications forAutomated DifferentialCell Counters forImmature or AbnormalBlood Cells - Precision(Section 9)	None	Site-to-site variability forCD3+CD4+ percentages andabsolute counts were found to beacceptable
Study	Testing Approach	FDA GuidanceDocuments	Standards/ References	Testing Results
AdultReference Interval	Establish adult reference intervals for lymphocytesubset analysis on theNavios EX Flow CytometrySystem.	Special Controls GuidanceDocument: PremarketNotifications forAutomated DifferentialCell Counters forImmature or AbnormalBlood Cells - ReferenceValues (Section 14)	EP28-A3c, Defining, Establishing,and Verifying Reference Intervalsin the Clinical Laboratory;Approved Guideline – ThirdEdition.	Adult reference intervals wereestablished and confirmed to beconsistent with published valuesfor T, B, and NK lymphocytesubsets.

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Substantial Equivalence Conclusion to Demonstrate Safety, Effectiveness & Equivalent Performance to Predicate:

The Navios EX Flow Cytometry System, that is the subject of this submission, in concert with the conclusions drawn from the performance testing discussed above demonstrate that when compared to the predicate device is as safe, as effective, and meets the performance acceptance criteria.

In summary, the Navios EX Flow Cytometry System as described in this submission is substantially equivalent in terms of safety and effectiveness to its predicate devices.

. The Navios EX Flow Cytometer, Navios EX tetra software, and tetraCHROME reagents are substantially equivalent to the Navios Flow Cytometer, Navios tetra software, and tetraCHROME reagents.
This summary of safety and effectiveness is being submitted in accordance with the requirements of the Safe Medical Device Act of 1990 and the implementing regulation 21 CFR 807.92.

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.”