(249 days)
Not Found
No
The document describes a flow cytometer and associated software for immunophenotyping. While it mentions "minor changes to the Navios EX tetra algorithm," there is no indication or mention of AI or ML being used in this algorithm or any other part of the system. The performance studies focus on traditional analytical performance characteristics of a flow cytometry system.
No
This device is an in vitro diagnostic device used for immunophenotyping, specifically for the identification and enumeration of lymphocyte percentages and absolute counts, which aids in the immunologic assessment of patients. It does not directly treat or prevent a disease.
Yes
Justification: The "Intended Use / Indications for Use" section explicitly states, "The Navios EX Flow Cytometer is intended for use as an in vitro diagnostic device for immunophenotyping..." and "The Navios EX tetra Software is intended for use as an in vitro diagnostic device for immunophenotyping...". It further specifies its use for the "identification and enumeration of CD3+CD4+, CD3+CD8+, CD3+, CD19+ and CD3-CD56+ lymphocyte percentages and absolute counts in peripheral whole blood" and is "indicated for use in the immunologic assessment of patients having or suspected of having immune deficiency," all of which fall under typical diagnostic activities.
No
The device description explicitly lists multiple hardware components as part of the "Navios EX Flow Cytometry System," including the "Navios EX Flow Cytometer" itself, reagents, fluorospheres, and workstations. While software is a component, the system is not solely software.
Yes, this device is an IVD (In Vitro Diagnostic).
The "Intended Use / Indications for Use" section explicitly states: "The Navios EX Flow Cytometer is intended for use as an in vitro diagnostic device for immunophenotyping..." and "The Navios EX tetra Software is intended for use as an in vitro diagnostic device for immunophenotyping...".
This clearly indicates that the device and its associated software are designed and intended for use in diagnostic procedures performed outside of the body (in vitro).
N/A
Intended Use / 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 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.
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.
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.
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.
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.
Product codes (comma separated list FDA assigned to the subject device)
OYE, PDX
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
Mentions image processing
Not Found
Mentions AI, DNN, or ML
Not Found
Input Imaging Modality
Flow cytometry
Anatomical Site
Peripheral whole blood
Indicated Patient Age Range
patients having or suspected of having immune deficiency. (Implied for all ages for whom such assessments are relevant, no specific age range given).
Intended User / Care Setting
Not Found
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
Not Found
Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)
- Laser Performance Characteristics: Verify stability of the laser performance of the Navios EX flow cytometer over time. Analysis of the data collected demonstrates that the Navios EX laser performance is stable over time.
- Instrument Carryover: To verify carryover using Flow-Check Pro fluorospheres meets performance specifications. Analysis of the data collected demonstrates that the Navios EX meets the carryover performance requirements.
- Instrument Linearity: Verify fluorescence detection is linear using standard Navios EX settings. Linearity of fluorescence measurements was demonstrated.
- Assay Carryover: To verify carryover of whole blood and reagents on the Navios EX meets performance specifications. Analysis of the data collected demonstrates that the Navios EX meets carryover performance requirements.
- Assay Linearity: Verify the linear range of the absolute values for each lymphocyte subset populations on the Navios EX Flow Cytometry System. Analysis of the data collected demonstrates that the Navios EX meets the linearity performance requirements.
- Detection Capability: To verify that the Navios EX meets the performance requirements for Limit of Blank (LoB), Limit of Detection (LoD), Limit of Quantitation (LLoQ). Analysis of the data collected demonstrates that the Navios EX meets the performance requirements for LOB, LOD, and LOQ in whole blood.
- Specimen and Prepared Sample Stability: Stability of whole blood samples will be evaluated to verify specimen and prepared sample stability claims. Analysis of the data collected demonstrates that the Navios EX Flow Cytometry System meets the requirements for specimen and prepared sample stability.
- Analytical Measuring Interval: Establish the Navios EX Analytical Measuring Interval (AMI) based on the system's capability (Linearity, Limit of Quantitation (LOQ)), consideration of the predicate and the application's intended use population. AMI of the Navios EX was verified to meet the 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. Analysis of the data collected demonstrates that the Navios EX Flow Cytometry System meets the performance requirements when compared to the predicate device.
- Precision – Across Model Configurations: Demonstrate system imprecision using control material as a surrogate for a stabilized sample on each of the three Navios EX configurations. Analysis of the data collected demonstrates that the Navios EX meets performance requirements.
- Method Comparison: To evaluate bias between the subject device versus the predicate. Analysis of the data collected demonstrates that the Navios EX Flow Cytometry System meets the performance requirements when compared to the predicate device.
- Precision — Long Term Imprecision: Demonstrate system imprecision using control material as a surrogate for a stabilized sample. Analysis of the data collected demonstrates that the Navios EX meets performance requirements for Long Term Imprecision.
- Precision — Whole Blood Repeatability: Evaluate sample imprecision using a precision profile approach to estimate repeatability at various medical decision levels and data percentiles. Analysis of the data collected demonstrates that the Navios EX meets performance requirements for Whole Blood Repeatability.
- Precision — Whole Blood Repeatability – Site To Site Variability: Evaluate site-to-site variability performance of CYTO-STAT tetraCHROME reagents for CD3+CD4+ percentage and absolute counts using whole blood specimens. Site-to-site variability for CD3+CD4+ percentages and absolute counts were found to be acceptable.
- Adult Reference Interval: Establish adult reference intervals for lymphocyte subset analysis on the Navios EX Flow Cytometry System. Adult reference intervals were established and confirmed to be consistent with published values for T, B, and NK lymphocyte subsets.
Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)
Not Found
Predicate Device(s): If the device was cleared using the 510(k) pathway, identify the Predicate Device(s) K/DEN number used to claim substantial equivalence and list them here in a comma separated list exactly as they appear in the text. List the primary predicate first in the list.
Reference Device(s): Identify the Reference Device(s) K/DEN number and list them here in a comma separated list exactly as they appear in the text.
Not Found
Predetermined Change Control Plan (PCCP) - All Relevant Information for the subject device only (e.g. presence / absence, what scope was granted / cleared under the PCCP, any restrictions, etc).
Not Found
§ 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.”
0
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
1
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
2
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
3
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.
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
4
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.
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
5
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.
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
6
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 | Date
Cleared | Classification | 21 CFR | Product
Code |
|-----------------------|------------------|-----------------|----------------|----------|-----------------|
| 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
7
- 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:
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
8
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 vitro
diagnostic device for immunophenotyping. It can be used in
conjunction with the following monoclonal antibody reagents
and 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 antibody
reagents. These reagents provide 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 flow cytometer using Flow-Count
Fluorospheres (single platform technology method) or
separate hematology results (dual platform method). These
reagents are indicated for use in the immunologic
assessment of patients having or suspected of having
immune deficiency. Navios tetra Software for automated analysis and results
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.
Navios Software may be installed on an independent computer
workstation for off-line analysis of listmode files generated by the
Navios Flow Cytometer with the monoclonal antibody reagents
and software package listed above. The off-line analysis must be
performed in accordance with the product labeling. | Similar – Differences are underlined:
The Navios EX Flow Cytometer is intended for use as an in vitro
diagnostic device for immunophenotyping using up to four
fluorescent detection channels with 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. |
| 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 |
| Software
Architecture | 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 |
| | tetraCHROME
Reagent Assay | |
| tetraCHROME
Reagents specimen
and prepared sample
stability claims | • Specimen stability - 24 hours room temperature
• Prepared sample stability
◦ 2 hours room temperature
◦ 24 hours refrigerated temperature | Same |
| | Sample Preparation
with Monoclonal
Antibodies | 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 of
prepared sample
prior to introduction
to 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 Parameter
Detectors | Six (FS, SS, FL1 - FL4) | Same |
| Electronics | 40 MHz sampling
Digital 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 with
dichroic filters. | Same |
| On-board analysis
software | System Software available | Same with minor modifications made to accommodate the new
laser |
| Off-line analysis
software | Off-line Software package available | Same with minor modifications made to accommodate the new
laser |
| Analysis Algorithm | Tetra analysis software available | Same with minor modifications implemented to address
differences 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 Cycle
Between Samples | Executed with IsoFlow Sheath Fluid ensuring carryover
specification is met | Same |
| Quality Control
Techniques | • Daily Instrument Checks
• Commercial Controls
• Inter-laboratory Quality Assurance Program (IQAP) | Same |
| Cleanse Cycle | Cleaning cycle performed with FlowClean cleaning reagent as
part of the daily shutdown process, before and after running
samples with vital dyes that stain the tubing, and as part of
troubleshooting. | Same |
| Compensation and Sample Preparation Reagents | | |
| Reagents used for
compensation and
sample preparation | CYTO-COMP Cell Kit
IMMUNOPREP Reagent System
QuickCOMP2 and 4 Kits
CytoTrol Cells | Same with the exception of not using CytoTrol |
| Controls and Calibrators | | |
| Assay Controls and
Calibrators | Flow-Check Pro Fluorospheres
Flow-Count Fluorospheres
Flow-Set Pro Fluorospheres
IMMUNO-TROL Cells
IMMUNO-TROL Low Cells | Same |
| Attribute | Navios Flow Cytometer
(Predicate)
K130373 | New Navios EX Flow Cytometer
(Subject Device) |
| Pre-Analytic Features | | |
| Sample Aspiration
Probe | Fixed height | Adjustable (by Beckman Coulter field service personnel) |
| Analytical Features | | |
| Lasers / Driver
Boards | 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 Light
Scatter | • 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 forward
scatter 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: two
thermoelectric devices at the top and bottom of the optics
module box | New Flow Cell with modified channel size and sheath flow
pressure. No gel coupling of the lens and optics module
temperature management hardware modified. |
| Fluorescence
collection | Collection lens and light path
• 1st and 2nd lens set:
o Gel coupled to flow cell, numerical aperture (NA)=1.2
o Light passes through optical fiber to PMT area
o Light leaves the fiber and is collimated
o Collimated light is separated by filters into desired bands
PMTs detect light and convert to electrical signals | Collection lens and light path:
• Spherical mirror and aspheric Schmidt lens
o No gel coupling, NA=1.2.
o Light passes through optical fiber to PMT area
o Light leaves the fiber and is collimated
o Collimated light is separated by filters into desired bands
PMTs 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 Light
Scatter | 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:
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.
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Summary of Navios EX Flow Cytometer Performance Testing
| Study | Testing Approach | FDA Guidance
Documents | Standards/ References | Testing Results |
|-------------------------------------------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Laser
Performance
Characteristics | Verify stability of the laser
performance of the Navios
EX flow cytometer over
time. | None | None | Analysis of the data collected
demonstrates that the Navios EX
laser performance is stable over
time. |
| Instrument
Carryover | To verify carryover using
Flow-Check Pro
fluorospheres meets
performance specifications. | Special Controls Guidance
Document: Premarket
Notifications for
Automated Differential
Cell Counters for
Immature or Abnormal
Blood Cells - Carryover
(Section 12) | CLSI H26-A2; FDA Standards
Recognition #7-210 | Analysis of the data collected
demonstrates that the Navios EX
meets the carryover performance
requirements. |
| Instrument
Linearity | Verify fluorescence
detection is linear using
standard Navios EX settings. | None | None | Linearity of fluorescence
measurements was
demonstrated. |
| Assay
Carryover | To verify carryover of whole
blood and reagents on the
Navios EX meets
performance specifications. | Special Controls Guidance
Document: Premarket
Notifications for
Automated Differential
Cell Counters for
Immature or Abnormal
Blood Cells - Carryover
(Section 12) | Validation, Verification, and
Quality Assurance of Automated
Hematology Analyzers, Approved
Standard - 2nd Edition; June
2010; CLSI H26-A2; FDA
Standards Recognition #7-210 | Analysis of the data collected
demonstrates that the Navios EX
meets carryover performance
requirements. |
| Study | Testing Approach | FDA Guidance
Documents | Standards/ References | Testing Results |
| Assay Linearity | Verify the linear range of the
absolute values for each
lymphocyte subset
populations on the Navios
EX Flow Cytometry System. | Special Controls Guidance
Document: Premarket
Notifications for
Automated Differential
Cell Counters for
Immature or Abnormal
Blood Cells - Linearity
(Section 11) | Evaluation of the Linearity of
Quantitative Measurement
Procedures: A Statistical
Approach; Approved Guideline;
April 2003. CLSI EP06-A; FDA
Standards Recognition #7-193 | Analysis of the data collected
demonstrates that the Navios EX
meets the linearity performance
requirements. |
| Detection
Capability | To verify that the Navios EX
meets the performance
requirements for Limit of
Blank (LoB), Limit of
Detection (LoD), Limit of
Quantitation (LLoQ). | None | Evaluation of Detection
Capability for Clinical Laboratory
Measurement Procedures;
Approved Guideline - Second
Edition; CLSI EP17-A2; FDA
Standards Recognition #7-233 | Analysis of the data collected
demonstrates that the Navios EX
meets the performance
requirements for LOB, LOD, and
LOQ in whole blood. |
| Specimen and
Prepared
Sample
Stability | Stability of whole blood
samples will be evaluated to
verify specimen and
prepared sample stability
claims. | None | None | Analysis of the data collected
demonstrates that the Navios EX
Flow Cytometry System meets the
requirements for specimen and
prepared sample stability. |
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| Study | Testing Approach | FDA Guidance
Documents | Standards/ References | Testing Results |
|----------------------------------------------------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Analytical
Measuring
Interval | Establish the Navios EX
Analytical Measuring
Interval (AMI) based on the
system's capability
(Linearity, Limit of
Quantitation (LOQ)),
consideration of the
predicate and the
application's intended use
population. | None | None | AMI of the Navios EX was verified
to meet the 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. | Special Controls Guidance
Document: Premarket
Notifications for
Automated Differential
Cell Counters for
Immature or Abnormal
Blood Cells - Accuracy
(Section 8) | Validation, Verification, and
Quality Assurance of Automated
Hematology Analyzers, Approved
Standard – 2nd Edition; June
2010; CLSI H26-A2; FDA
Standards
Recognition # 7-210
CLSI EP09-A3, Method
Comparison and Bias Estimation
Using Patient Samples; Approved
Guideline--Second Edition
(Interim Revision) | Analysis of the data collected
demonstrates that the Navios EX
Flow Cytometry System meets the
performance requirements when
compared to the predicate device. |
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| Study | Testing Approach | FDA Guidance
Documents | Standards/ References | Testing Results |
|------------------------------------------------------------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Precision –
Across Model
Configurations | Demonstrate system
imprecision using control
material as a surrogate for a
stabilized sample on each of
the three Navios EX
configurations. | Special Controls Guidance
Document: Premarket
Notifications for
Automated Differential
Cell Counters for
Immature or Abnormal
Blood Cells - Precision
(Section 9) | CLSI EP05-A2, Evaluation of
Precision Performance of
Quantitative Measurement
Methods; Approved Guideline –
Second Edition. | Analysis of the data collected
demonstrates that the Navios EX
meets performance requirements. |
| Method
Comparison | To evaluate bias between
the subject device versus
the predicate. | Special Controls Guidance
Document: Premarket
Notifications for
Automated Differential
Cell Counters for
Immature or Abnormal
Blood Cells - Accuracy
(Section 8) | Validation, Verification, and
Quality Assurance of Automated
Hematology Analyzers, Approved
Standard – 2nd Edition; June
2010; CLSI H26-A2; FDA
Standards
Recognition # 7-210
CLSI EP09-A3, Method
Comparison and Bias Estimation
Using Patient Samples; Approved
Guideline–Second Edition
(Interim Revision) | Analysis of the data collected
demonstrates that the Navios EX
Flow Cytometry System meets the
performance requirements when
compared to the predicate device. |
| Study | Testing Approach | FDA Guidance
Documents | Standards/ References | Testing Results |
| Precision —
Long Term
Imprecision | Demonstrate system
imprecision using control
material as a surrogate for a
stabilized sample | Special Controls Guidance
Document: Premarket
Notifications for
Automated Differential
Cell Counters for
Immature or Abnormal
Blood Cells - Precision
(Section 9) | CLSI EP05-A2, Evaluation of
Precision Performance of
Quantitative Measurement
Methods; Approved Guideline -
Second Edition. | Analysis of the data collected
demonstrates that the Navios EX
meets performance requirements
for Long Term Imprecision. |
| Precision —
Whole Blood
Repeatability | Evaluate sample imprecision
using a precision profile
approach to estimate
repeatability at various
medical decision levels and
data percentiles. | Special Controls Guidance
Document: Premarket
Notifications for
Automated Differential
Cell Counters for
Immature or Abnormal
Blood Cells - Precision
(Section 9) | CLSI H26-A2, Validation,
Verification, and Quality
Assurance of Automated
Hematology Analyzers
CLSI EP05-A2, Evaluation of
Precision Performance of
Quantitative Measurement
Methods; Approved Guideline -
Second Edition. | Analysis of the data collected
demonstrates that the Navios EX
meets performance requirements
for Whole Blood Repeatability. |
| Precision —
Whole Blood
Repeatability
– Site To Site
Variability | Evaluate site-to-site
variability performance of
CYTO-STAT tetraCHROME
reagents for CD3+CD4+
percentage and absolute
counts using whole blood
specimens | Special Controls Guidance
Document: Premarket
Notifications for
Automated Differential
Cell Counters for
Immature or Abnormal
Blood Cells - Precision
(Section 9) | None | Site-to-site variability for
CD3+CD4+ percentages and
absolute counts were found to be
acceptable |
| Study | Testing Approach | FDA Guidance
Documents | Standards/ References | Testing Results |
| Adult
Reference Interval | Establish adult reference intervals for lymphocyte
subset analysis on the
Navios EX Flow Cytometry
System. | Special Controls Guidance
Document: Premarket
Notifications for
Automated Differential
Cell Counters for
Immature or Abnormal
Blood Cells - Reference
Values (Section 14) | EP28-A3c, Defining, Establishing,
and Verifying Reference Intervals
in the Clinical Laboratory;
Approved Guideline – Third
Edition. | Adult reference intervals were
established and confirmed to be
consistent with published values
for T, B, and NK lymphocyte
subsets. |
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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.