(249 days)
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.
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
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.
§ 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.”