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The DxFLEX Flow Cytometer is intended for use as an in vitro diagnostic device for immunophenotyping using up to ten fluorescent detection channels using three lasers (488 nm, 638 nm and 405 nm) 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 ClearLab 10C Panels are intended for in vitro diagnostic use for qualitative identification of cell populations by multiparameter immunophenotyping on the Navios, Navios EX and DxFLEX flow cytometers. These reagents are used as an aid in the differential diagnosis of hematologically abnormal patients having, or suspected of having, the following hematopoietic neoplasms: chronic leukemia, acute leukemia, non-Hodgkin lymphoma, myelodysplastic syndrome (MDS), and/or myeloproliferative neoplasms (MPN). The reagents can be used with peripheral whole blood (collected in K2EDTA, Acid Citrate Dextrose (ACD) or Heparin), bone marrow (collected in K2EDTA, ACD or Heparin) and lymph node specimens. Interpretation of the results should be confirmed by a pathologist or equivalent professional in conjunction with other clinical and laboratory findings.

These reagents provide multiparameter, qualitative results for the surface antigens listed below:

• ClearLLab 10C B Cell Tube: Kappa, Lambda, CD10, CD5, CD200, CD34, CD38, CD20, CD19, CD45
• ClearLLab 10C T Cell Tube: TCRy6, CD4, CD2, CD56, CD5, CD34, CD3, CD8, CD7, CD45
• ClearLLab 10C M1 Cell Tube: CD16, CD7, CD10, CD13, CD64, CD34, CD14, HLA-DR, CD11b, CD45
• ClearLLab 10C M2 Cell Tube: CD15, CD123, CD117, CD13, CD33, CD34, CD38, HLA-DR, CD19, CD45

The ClearLLab 10C Reagent System is currently cleared on the Navios EX Flow cytometer under K183592. Beckman Coulter has developed the DxFLEX Flow Cytometer, a next generation flow cytometer that offers enhanced performance in terms of optics and electronics, as well as more convenient installation and operation. The indications for use of the ClearLLab 10C Reagent System will be expanded to include its use on the DxFLEX Flow Cytometer. Furthermore, the indications for use will be clearly stated on labeling. The intended use of the ClearLLab 10C Reagent System will not be modified.

ClearLLab 10C Reagent System components that are included with use on the DxFLEX Flow Cytometer:

• DxFLEX Flow Cytometer [3 laser/10 color configuration] [New]
• DxFLEX Daily OC Fluorospheres [New]
• ClearLLab 10C Panels [B, T, M1 and M2] [Modification to Existing]
• ClearLLab Compensation Kit [Modification to Existing]
• ClearLLab Compensation Beads [Modification to Existing]
• ClearLLab Control Cells, normal and abnormal [Modification to Existing]
• Kaluza C data analysis software [Existing]
• IOTest 3 Fixative Solution [Existing]
• IOTest 3 Lysing Solution [Existing]

The ClearLLab 10C Reagent System is run on Beckman Coulter's DxFLEX Flow Cytometer (3 Laser/10 Color configuration]. The DxFLEX Flow Cytometer includes the hardware and CytExpert for DxFLEX software. It requires off-line manual sample processing and use of the accompanying lysing reagent. As part of the ClearLLab 10C Reagent System, to allow proper utilization of this applications for the DxFLEX flow cytometers include ten fluorescent detection channels (FL1-FL10) and three laser configurations (blue, red and violet).

As with the workflow on the predicate system, LMD data analysis is performed manually using the Kaluza C Analysis Software. This Analysis Software package is supplied separately from the DxFLEX and must be installed on an independent computer workstation for off-line analysis of listmode files generated on the flow cytometer with the associated reagents and cytometer system software package, including Control Cell QC data and sample data analysis. The CvtExpert for DxFLEX software is NOT be recommended for analysis use with this application (Note that OC data DxFLEX Daily OC Fluorospheres and Compensation products will continue to be analyzed using the on-board instrument software).

Kaluza C Software is a software tool designed to work with *.fcs and *.lmd files generated from flow cytometers. The advantages of using the Kaluza C over the CytExpert for DxFLEX software are listed below:

• Powerful processing speed allows fast analysis of listmode data, including real-time updating of gating and compensation
• Plot displays are more versatile allowing linear, logarithmic and 'Logicle' (linear/log hybrid) axes as well as configurable scaling and zooming options
• Range of compensation options
• QC reporting includes Levey-Jennings plots and highlighted pass/fail criteria on results displays

Preset Kaluza C analysis templates for the ClearLLab 10C reagent system will be provided. The total WBC gate is defined in the histogram of SS vs. CD45-KO525-A by the inclusion of all CD45+ events with low, medium and high Side Scatter after the exclusion of the cells that were compromised and/or aggregated. A subsequent histogram defines specific leukocyte subset such as lymphocytes, monocytes, granulocytes. The low SS/bright CD45+ population identifies lymphocytes. Applicable markers are then displayed in subsequent histograms gated on lymphocytes. This process is repeated for mid SS/medium CD45+ populations to identify monocytes and for high SS/medium CD45+ to identify granulocytes.

The provided document describes the ClearLLab 10C Reagent System on the DxFLEX Flow Cytometer and its substantial equivalence to the predicate device, the ClearLLab 10C Reagent System on the Navios EX Flow Cytometer.

Here's an analysis of the acceptance criteria and study data based on the provided text:

1. Table of Acceptance Criteria and Reported Device Performance

The document doesn't explicitly present a single table labeled "Acceptance Criteria" and "Reported Device Performance" side-by-side with specific numerical thresholds for each criterion. Instead, it lists various studies, their objectives, and the "Testing Results" which indicate whether the device met the performance requirements.

However, we can infer the acceptance criteria from the objectives of the studies and the "Testing Results" column. The reported device performance is stated as meeting these requirements.

Additional Requested Information:

• 2. Sample sized used for the test set and the data provenance (e.g. country of origin of the data, retrospective or prospective)

  • Sample Size: The document doesn't explicitly state the specific sample sizes for all test sets. For "Precision - Operator and Instrument Variability," it mentions "the same specimen prepared by three (3) operators, twice a day, on two (2) DxFLEX Flow Cytometers." For "Clinical Accuracy," it mentions "specimens from donors in the intended use population" evaluated in a "multi-site evaluation."
  • Data Provenance: The document does not specify the country of origin of the data. The "Clinical Accuracy" study states it used "specimens from donors in the intended use population," implying clinical samples. It does not state if the studies were retrospective or prospective, though "Multi-Site with Clinical Specimens" and "Clinical Accuracy" studies usually imply prospective collection for validation.

• 3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts (e.g. radiologist with 10 years of experience)

  • The document states for the "Indications for Use" of the ClearLLab 10C Panels: "Interpretation of the results should be confirmed by a pathologist or equivalent professional in conjunction with other clinical and laboratory findings."
  • However, regarding the studies themselves, and specifically for establishing the ground truth for the test set used in the evaluations (e.g., in the Clinical Accuracy study), the document does not specify the number of experts, their qualifications, or their role in establishing ground truth. The "Clinical Accuracy" study compared the DxFLEX system to the predicate Navios EX, implying the predicate's results served as a comparative reference rather than an independent expert ground truth being explicitly defined for the DxFLEX data.

• 4. Adjudication method (e.g. 2+1, 3+1, none) for the test set

  • The document does not describe any adjudication method used for the test set.

• 5. If a multi reader multi case (MRMC) comparative effectiveness study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance

  • This device is a flow cytometer and reagent system, not an AI-assisted diagnostic tool. Therefore, an MRMC comparative effectiveness study involving human readers and AI assistance is not applicable and was not performed or mentioned in this document. The "Clinical Accuracy" study compared the new device to a predicate device, which is a different type of comparative study.

• 6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done

  • The device described is an in vitro diagnostic device (flow cytometer and reagents) that generates qualitative data for immunophenotyping. The data analysis uses "Kaluza C data analysis software," but the "Interpretation of the results should be confirmed by a pathologist or equivalent professional." This indicates it is not a standalone algorithm in the sense of providing a final diagnosis without human interpretation. Performance studies were largely focused on the instrument and reagent's analytical capabilities, not a standalone diagnostic algorithm.

• 7. The type of ground truth used (expert consensus, pathology, outcomes data, etc.)

  • For the "Clinical Accuracy" study, the ground truth was essentially implied by comparison to the predicate device (Navios EX flow cytometer). The study aimed to demonstrate "performance equivalency" and "qualitative immunophenotype agreement" between the DxFLEX system and the cleared Navios EX system. While pathologists confirm interpretations, the studies described herein validate the device's performance against established methods, rather than generating a de novo ground truth from pathology and outcomes for every case.

• 8. The sample size for the training set

  • The document does not mention a training set or its sample size. This type of submission (for a flow cytometer and reagent system) typically focuses on analytical and clinical validation studies, rather than machine learning model training.

• 9. How the ground truth for the training set was established

  • As no training set is mentioned, information on how its ground truth was established is not provided.

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The BD FACSLyric™ flow cytometer is intended for use as an in vitro diagnostic device for immunophenotyping using up to six fluorescence detection channels and two light scatter channels using a blue (488-nm) and a red (640-nm) laser. It is intended for use with in vitro diagnostic (IVD) assays and software that are indicated for use with the instrument.

The BD FACSLyric™ flow cytometer with the integrated BD FACSDuet™ System is intended for use as an in vitro diagnostic device for immunophenotyping using up to six fluorescence detection channels and two light scatter channels using a blue (488-nm) aser. It includes an automated sample preparation system used to prepare human peripheral whole blood samples for acquisition and analysis and is intended for use with in vitro diagnostic (IVD) assays and software that are indicated for use with the instrument.

The BD FACSLyric™ Flow Cytometer is a flow cytometer system. The BD FACSLyric™ Flow Cytometer with the integrated BD FACSDuet™ Sample Preparation System includes the flow cytometer and an automated sample preparation system. The system includes the BD FACSLyric™ Flow Cytometer, BD FACSTM Universal Loader, BD FACSuite™ Clinical software, BD FACSDuet™ Sample Preparation System, BD Multitest™ 6- Color and 4-Color Assay Modules, BD® FACSFlow™ Sheath Fluid, BD® CS&T Beads, and BD® FC Beads 7-Color Kit. It uses flow cytometry and immunofluorescence assay methodology.

Here's an analysis of the acceptance criteria and study data from the provided text, formatted as requested:

1. Table of Acceptance Criteria and Reported Device Performance

The document broadly states that "All acceptance criteria were met" or "The acceptance criteria were met" for each study, but it does not explicitly list the specific numerical acceptance criteria for each performance metric. It only provides the objective of each study.

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

• Whole Blood Repeatability: Used "HIV+ patient and normal whole blood specimens." The sample size for each group is not specified.
• Method Comparison: "A total of 399 enrolled specimens were tested across 3 sites." Data provenance (country of origin, retrospective/prospective) is not specified.
• Inter-laboratory Reproducibility: "variability across three sites." The number of samples for this study is not explicitly stated, but it likely overlaps with or is a subset of the 399 specimens from the Method Comparison study if performed at the same sites.
• Other analytical studies (Within-site Precision, Linearity, LoB/LoD, LoQ, In-Use Reagent Stability, Equivalency between Incubation Times, Specimen Carryover, Reagent Carryover, Pipette Dispense Accuracy and Precision) do not specify sample sizes or data provenance in the provided text.

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

Not applicable. This device is an automated differential cell counter (flow cytometer) for immunophenotyping. The performance studies described involve analytical measurements and comparisons between automated and manual sample preparation, not expert interpretation of outputs to establish ground truth in the same way an imaging AI might. Ground truth for immunophenotyping would typically be derived from the inherent properties of the biological samples or established reference methods.

4. Adjudication Method for the Test Set

Not applicable, as expert adjudication is not relevant for the type of performance studies described for this device.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done, and Effect Size of Human Readers Improvement with AI vs Without AI Assistance

Not applicable. An MRMC study is typically for evaluating the diagnostic performance of a device (often imaging AI) when used by human readers, and comparing performance with and without AI assistance. This device is an automated instrument with an automated sample preparation system, not an AI intended to assist human interpretation in a diagnostic workflow where "readers" are involved.

6. If a Standalone (Algorithm Only Without Human-in-the-Loop Performance) Was Done

Yes, the studies described are essentially "standalone" in the sense that they evaluate the performance of the automated system itself (the BD FACSLyric Flow Cytometer with the integrated BD FACSDuet Sample Preparation System) in performing immunophenotyping, either against its manually-prepared equivalent or against established analytical standards. There is no human-in-the-loop component described for these performance evaluations.

7. The Type of Ground Truth Used

The ground truth for the performance studies appears to be based on:

• Reference Methods/Established Standards: This is implied by adherence to CLSI (Clinical and Laboratory Standards Institute) guidelines (e.g., CLSI EP05-A3, CLSI EP6-A, CLSI EP17-A2, CLSI H26-A2, CLSI EP25-A, CLSI EP09c). These guidelines typically involve comparing the device's output to known values, spiked samples, or established reference systems.
• Comparison to Predicate Device: For the "Method Comparison" study, the ground truth is essentially the performance of the predicate device (FACSLyric flow cytometer with manual sample preparation), since the objective is to demonstrate equivalency with the new automated system.
• Inherent Sample Properties: For studies like "Whole Blood Repeatability," the ground truth is the expected inherent stability and consistency of measurements from the human whole blood specimens (HIV+ and normal).

8. The Sample Size for the Training Set

The document does not mention a "training set" as it would for a machine learning or AI device. The validation of the device's performance is described, but the underlying development and calibration data (which might be analogous to a training set for a traditional instrument) are not detailed.

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

As no "training set" is explicitly mentioned in the context of AI/ML, this question is not applicable. For traditional medical devices, the "ground truth" during development (which could be considered analogous to training) is typically established through rigorous analytical testing and adherence to predefined specifications and accepted scientific principles for instrument calibration and performance.

Ask a specific question about this device

The BD FACSLyric™ flow cytometer is intended for use as an in vitro diagnostic device for immunophenotyping using up to six fluorescence detection channels and two light scatter channels using a blue (488-nm) and a red (640-nm) laser. It is intended for use with in vitro diagnostic (IVD) assays and software that are indicated for use with the instrument.

BD Multitest™ 6-color TBNK, BD Multitest™ IMK kit, BD Multitest™ CD3/CD8/CD45/CD4, and BD Multitest™ CD3/CD16+CD56/CD45/CD19, all with optional BD Trucount™ tubes, are intended for use on the BD FACSLyric flow cytometer with peripheral whole blood for immunophenotyping. These reagents are indicated for use in the immunological assessment of normal individuals, and patients having, or suspected of having, immune deficiency. These reagents determine the percentages and absolute counts of the following mature human lymphocyte subsets:

BD Multitest 6-color TBNK with optional BD Trucount tubes

• · T lymphocytes (CD3+)
• · B lymphocytes (CD19+)
• · Natural killer (NK) lymphocytes (CD3-CD16+ and/or CD56+)
• · Helper/inducer T lymphocytes (CD3+CD4+)
• · Suppressor/cytotoxic T lymphocytes (CD3+CD8+)

BD Multitest IMK kit with optional BD Trucount tubes

• · T lymphocytes (CD3+)
• · B lymphocytes (CD19+)
• · Natural killer (NK) lymphocytes (CD3-CD16+ and/or CD56+)
• · Helper/inducer T lymphocytes (CD3+CD4+)
• · Suppressor/cytotoxic T lymphocytes (CD3+CD8+)

BD Multitest CD3/CD8/CD45/CD4 with optional BD Trucount tubes

• · T lymphocytes (CD3+)
• · Suppressor/cytotoxic T lymphocytes (CD3+CD8+)
• · Helper/inducer T lymphocytes (CD3+CD4+)

BD Multitest CD3/CD16+CD56/CD45/CD19 with optional BD Trucount tubes

• · T lymphocytes (CD3+)
• · Natural killer (NK) lymphocytes (CD3-CD16+ and/or CD56+)
• · B lymphocytes (CD3-CD19+)

The BD FACSLyric Flow Cytometer consists of the following components.

• FACSLyric Flow Cytometer (3-1, 4-2, 4-2-2 and 4-3-3 optical configurations)
• FACSuite Clinical Software
• Multitest 6-Color Assay Modules
• Multitest 4-Color Assay Modules
• FC Beads 7-Color Kit
• CS&T Beads
• Multitest 6-Color TBNK
• Multitest IMK Kit
• . Multitest CD3/CD8/CD45/CD4
• Multitest CD3/CD16+CD56/CD45/CD19
• . Multi-Check Control
• . Multi-Check CD4 Low Control
• . Trucount Tubes
• Optional FACS Universal Loader

The system is an immunofluorescence assay system for identification and enumeration of lymphocyte subsets in peripheral whole blood. When blood is added to the monoclonal antibody reagent, the fluorochrome-labeled antibodies in the reagent bind specifically to lymphocvte surface antigens. During acquisition, the cells travel past one or more laser beams in a single file and scatter the laser light. The stained cells fluoresce. The scatter and fluorescence light is detected by the flow cytometer, separated by dichroic mirrors and optical filters, and then quantified with photomultiplier tubes (PMTs) to determine the percent lymphocyte of particular cell populations.

Multiple monoclonal antibodies each labeled with a different fluorochrome are contained within one reagent tube to simultaneously identify multiple lymphocyte subset populations. The use of Trucount tubes provides the absolute number of the fluorochrome-labeled antibody bound cells.

The provided text describes the BD FACSLyric™ Flow Cytometer, its indications for use, comparison to a predicate device (BD FACSCanto™ II system), and performance data supporting its substantial equivalency. Based on the provided document, here's an analysis of the acceptance criteria and study proving device performance:

Important Note: This document is an FDA 510(k) summary, which focuses on demonstrating substantial equivalence to a legally marketed predicate device rather than strictly presenting a clinical study design with explicit acceptance criteria for a novel AI/ML device. Therefore, some information (e.g., number of experts, adjudication methods, MRMC study effect size, sample size for training set, ground truth for training set) typically available for AI/ML device studies may not be directly available or applicable in this context. The study described focuses on demonstrating the performance of a new flow cytometer instrument rather than an AI/ML algorithm.

1. Table of Acceptance Criteria and Reported Device Performance

The document defines acceptance criteria primarily through "Objectives" for each study and "Results" indicating whether these objectives were met. The acceptance criteria are largely based on meeting performance requirements that demonstrate equivalency to the predicate device or established clinical laboratory guidelines (CLSI standards).

• To demonstrate equivalency between FACSLyric Universal Loader (UL) acquisition and FACSLyric manual acquisition. | The method bias between the FACSLyric and the FACSCanto II met the acceptance criteria. Equivalency between FACSLyric UL acquisition and Manual acquisition was demonstrated. |
  | Within-site Precision | To evaluate the within-site precision performance of FACSLyric system using Multitest IMK kit and Multitest 6-Color TBNK with Trucount tubes (meeting within-run and total precision requirements). | All acceptance criteria were met. The within-site precision performance satisfied the within-run and total precision performance requirements. |
  | Whole Blood Repeatability | To verify repeatability performance across all FACSLyric instruments of different configurations, using whole blood from patient and normal donor samples, stained with reagents (all lymphocyte subsets meeting %CV and SD acceptance criteria). | Repeatability performance was demonstrated across all instruments with different configurations. All lymphocyte subsets met %CV and SD acceptance criteria. |
  | Linearity | To evaluate the linear range of the FACSLyric system using reagents (acceptable linear ranges established for each lymphocyte subset). | Acceptable linear ranges have been established for each lymphocyte subset for each of the Multitest reagents on FACSLyric system. |
  | Sample Carryover | To determine percent sample carryover (less than or equal to 0.1% for low carryover and less than or equal to 0.5% for standard carryover). | All results met the acceptance criteria (less than or equal to 0.1% for low carryover and less than or equal to 0.5% for standard carryover) on all three FACSLyric instruments. Single SIT flush sufficient for low carryover. |
  | Reagent Carryover | To verify minimal reagent carryover. | Results met the acceptance criteria. Amount of reagent carried over is well below the amount required for effective staining. |
  | Detection Capability of LoB and LoD | To evaluate the limit of blank (LoB) and limit of detection (LoD) (LoB and LoD for CD4 lymphocyte subset absolute counts less than 50 cells/µL). | LoB and LoD for CD4 lymphocyte subset absolute counts were established and were less than 50 cells/µL. |
  | Detection Capability of LoQ | To evaluate the limit of quantitation (LoQ) (LoQ for CD4 lymphocyte subset absolute counts less than 50 cells/µL). | The LoQ for the CD3+, CD3+CD4+, CD3+CD8+, CD19+, CD16+CD56+ and CD45+ lymphocyte subsets were established. Acceptance criteria were met and the LOQ is less than 50 cells/µL for CD4 lymphocyte subset absolute counts. |
  | Setup and QC Performance | To verify that Setup & QC Performance meets pre-defined specifications. | All Setup & QC performance results met the acceptance criteria. |
  | Setup and QC Stability | To verify the stability of system level Setup & QC. | All system level Setup & QC stability performance results met the pre-defined specifications. |
  | Clinical Performance: | | |
  | Method Comparison | To evaluate performance equivalence of the FACSLyric system and the FACSCanto II system on the determination of lymphocyte subsets. | The acceptance criteria for all lymphocyte subsets were met for the FACSLyric system. Differences were minimal and no bias trend observed when comparing manipulated vs non-manipulated specimens or different EDTA formulations. |
  | Inter-laboratory Reproducibility | To evaluate inter-laboratory reproducibility for the FACSLyric system (variability for within run, between run, between day, between site, and total precision meeting 97.5% one-sided confidence interval compared to requirements). | Inter-laboratory reproducibility was carried out at four clinical sites. Variability met requirements and 97.5% one-sided confidence interval on precision was estimated and compared. |
  | Reference Intervals | To re-establish the reference intervals of a normal male and female adult cohort (reference intervals established for all lymphocyte subsets). | Reference Intervals for all lymphocyte subsets were established. Differences observed between genders were not clinically significant. |
  | Specimen Stability | To generate data to support stability of venous whole blood with EDTA anticoagulant when testing reagents on the FACSLyric system (supporting stability claims for Age of Blood and Age of Stain). | The results support the claim of up to 24 hours Age of Blood and 6 hours Age of Stain for Multitest 6-Color TBNK, and up to 48 hours Age of Blood and 24 hours Age of Stain for Multitest IMK kit (including other Multitest assays) on FACSLyric system. |

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

• Inter-instrument Optical Configuration Equivalency & Whole Blood Repeatability: Used patient and normal donor samples from unspecified locations.
• Method Comparison (Bench Study): Samples sourced from unspecified locations.
• Method Comparison (Clinical Study): A total of 332 specimens were enrolled for Multitest 6-Color TBNK (297 evaluable), and 368 specimens were enrolled for Multitest IMK kit (336 evaluable) at 5 clinical sites. These were remnant, de-linked patient specimens. The provenance is not explicitly stated as retrospective or prospective, but "remnant, de-linked patient specimens" typically implies a retrospective use of existing samples.
• Inter-laboratory Reproducibility: Used a single lot of Streck CD-Chex Plus process control material at four clinical sites. (Not a human patient sample size).
• Reference Intervals: A total of 136 subjects were enrolled (134 evaluable for Multitest 6-Color TBNK and 130 evaluable for Multitest IMK kit) from one clinical site. These were prospectively procured and de-linked donor specimens.
• Specimen Stability: A total of 227 specimens were enrolled for each of the reagents from two clinical sites. These were prospectively procured and de-linked patient specimens.

Data Provenance (General): While specific countries are not mentioned, the document is an FDA submission for the US market, implying that the studies were conducted in accordance with US regulatory requirements, likely involving US-based clinical sites. The data included both normal donor and patient samples, and were both prospectively and retrospectively collected (e.g., remnant, de-linked specimens).

3. Number of Experts Used to Establish Ground Truth and Qualifications:

This document describes a flow cytometer and associated reagents, not an AI/ML algorithm that requires expert labeling of images or complex data for ground truth. The "ground truth" for this type of device is the accurate measurement and enumeration of cell subsets, which is compared against results from a predicate device or validated laboratory methods. Therefore, the concept of "experts establishing ground truth for the test set" as typically understood in AI/ML validation studies (e.g., radiologists annotating images) is not directly applicable here. The accuracy of the cell counts would be intrinsically tied to the performance of the predicate device (BD FACSCanto II system) and the established clinical laboratory guidelines (CLSI standards) used for comparison.

4. Adjudication Method for the Test Set:

Not applicable in the context of this device and study type. The studies involve quantitative measurements and comparisons against established parameters or a predicate device, rather than subjective interpretations requiring adjudication among multiple readers.

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

No, an MRMC comparative effectiveness study, as typically done for AI/ML devices assisting human readers in diagnostic tasks, was not conducted or described. This submission relates to a flow cytometer instrument, where performance is measured by its ability to accurately count and phenotype cells, rather than its effect on human interpretations of complex data like medical images.

6. Standalone (Algorithm Only) Performance:

Not applicable. The device is a "Flow Cytometer," an automated instrument for in vitro diagnostic use. Its performance is inherently "standalone" in executing its function of cell counting and phenotyping. There is no separate "algorithm-only" component as might be found in an AI/ML software. The software (FACSuite Clinical Software) manages the instrument and data analysis for the user, and its performance is evaluated as part of the overall system.

7. Type of Ground Truth Used:

The ground truth is established by:

• Predicate Device Comparison: The performance of the BD FACSLyric™ system is compared to a legally marketed predicate device, the BD FACSCanto™ II system. This is a primary form of "ground truth" for demonstrating substantial equivalence.
• Established Clinical Laboratory Standards: Adherence to various Clinical and Laboratory Standards Institute (CLSI) guidelines (e.g., CLSI EP09-A3 for Method Comparison and Bias Estimation, CLSI EP05-A3 for Precision, CLSI EP6-A for Linearity, CLSI H26-A2 for Carryover, CLSI EP17-A2 for Detection Capability, CLSI EP28-A3c for Reference Intervals) serves as the "ground truth" for acceptable analytical performance. These standards provide accepted methodologies and performance metrics for laboratory assays.
• Quantitative Measurement: The device measures percentages and absolute counts of lymphocyte subsets. The "ground truth" for these measurements is the true biological count in the sample, which is assessed through rigorous validation encompassing precision, linearity, limits of detection, and comparison to a well-characterized predicate.

8. Sample Size for the Training Set:

Not applicable. This is not an AI/ML device, and there is no mention of a "training set" for an algorithm. The development and validation of flow cytometers rely on engineering principles, analytical studies, and clinical performance studies, not on training data for a machine learning model.

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

Not applicable, as there is no training set for an AI/ML algorithm.

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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

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.

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The AQUIOS CL Flow Cytometer is intended for use with in vitro diagnostic flow cytometric applications using up to four fluorescent detection channels using a blue (488 mm) laser, two light scatter detection volume (EV). It is used in conjunction with the following reagents and software package.

AQUIOS Tetra-1 Panel and AQUIOS Tetra-2+ Panel monoclonal antibody reagents are for use on the AQUIOS CL Flow Cytometer with peripheral whole blood for immunophenotyping. These reagents are indicated for use in the immunologic assessment of patients having, or suspected of having, immune deficiency. These reagents provide identification and enumeration of;

• AQUIOS Tetra-1 Panel Monoclonal Antibody Reagent

· Total CD3+, CD3+CD4+,CD3+CD3+, CD3+CD4+/CD3+CD8+ (ratio only) lymphocyte percentages and absolute counts.

• CD45+ absolute count

• · CD45+ Low SS (lymphocytes) percentage and absolute count
  AQUIOS Tetra-2+ Panel Monoclonal Antibody Reagent

• · Total CD3+, CD3-CD19+, CD3-CD56+ and/or CD16+ lymphocyte percentages and absolute counts.

• CD45+ absolute count

• · CD45+ Low SS (lymphocytes) percentage and absolute count

AQUIOS Flow Cytometry Software may be run on an independent computer workstation for off-line analysis of results generated by the AQUIOS CL Flow Cytometer with the monoclonal antibody reagents listed above. The off-line analysis must be performed in accordance with the product labeling.

AQUIOS Tetra-1 Panel and AQUIOS Tetra-2+ Panel monoclonal antibody reagents are for use on the AQUIOS CL Flow Cytometer with peripheral whole blood for immunophenotyping. These reagents are indicated for use in the immunologic assessment of patients having, or suspected of having, immune deficiency. These reagents provide identification and enumeration of;

• AQUIOS Tetra-1 Panel Monoclonal Antibody Reagent

· Total CD3+, CD3+CD4+,CD3+CD8+, CD3+CD4+/CD3+CD8+(ratio only) lymphocyte percentages and absolute

counts.

• CD45+ absolute count
• · CD45+ Low SS (lymphocytes) percentage and absolute count
• AQUIOS Tetra-2+ Panel Monoclonal Antibody Reagent
• · Total CD3+, CD3-CD19+, CD3-CD56+ and/or CD16+ lymphocyte percentages and absolute counts.
• CD45+ absolute count
• · CD45+ Low SS (lymphocytes) percentage and absolute count

AQUIOS IMMUNO-TROL Cells are assayed, lysable whole blood quality control product for immunophenotyping analysis using monoclonal antibody reagents and flow cytometry. It provides a positive cell control that is processed in the same manner as a whole blood sample. This allows verification of instrument and reagent performance. It also verifies the methods used for staining targeted cells, lysing erythrocytes, and analyzing samples by the AQUIOS CL Flow Cytometer.

AQUIOS IMMUNO-TROL Low Cells are assayed, lysable whole blood quality control product for immunophenotyping analysis using monoclonal antibody reagents and flow cytometry. It provides a positive cell control that is processed in the same manner as a whole blood sample. This allows verification of instrument and reagent performance. It also verifies the methods used for staining targeted cells, lysing erythrocytes, and analyzing samples by the AQUIOS CL Flow Cytometer.

AQUIOS Lysing Reagent Kit is used as part of the AQUIOS flow cytometer system. The kit consists used by AQUIOS flow cytometers to prepare whole blood samples for analysis of white blood cells.

The AQUIOS CL Flow Cytometry System is composed of the following components:

• . AQUIOS CL Flow Cytometer
• AQUIOS System Software ●
• AQUIOS Tetra-1 Panel CD45-FITC/CD4-RD1/CD8-ECD/CD3-PC5 ●
• AQUIOS Tetra-2+ Panel CD45-FITC/(CD56+CD16)-RD1/CD19-ECD/CD3-PC5 ●
• AQUIOS Immuno-Trol Cells ●
• AQUIOS Immuno-Trol Low Cells ●
• . AQUIOS Lysing Reagent Kit

The AQUIOS CL Flow Cytometer uses flow cytometric principles to determine qualitative and quantitative measurements of biological and physical properties of cells and other particles. These properties are measured when the cells pass through the laser beam(s) in single file.

The AQUIOS System Software is designed for the AQUIOS CL flow cytometer. It includes the algorithms and test definitions that provide automated analysis and results for AQUIOS Tetra-1 and 2+ reagents; this application cannot be modified by the user.

The AQUIOS Flow Cytometry System also offers an optional standalone offline workstation. This workstation is identical to the workstation that is physically connected to the instrument and can be used for off-line analysis of results generated by the AQUIOS CL Flow Cytometer with AQUIOS Tetra-1 and Tetra-2+ reagents and AQUIOS System software according to the product labeling.

AQUIOS Tetra-1 Panel CD45-FITC/CD4-RD1/CD8-ECD/CD3-PC5 reagent provides identification and enumeration of CD45+, CD45+ Low SS, and CD3+/CD4+, CD3+/CD8+, and CD3+ lymphocyte percentages and absolute counts in peripheral whole blood. AQUIOS Tetra-2+ Panel CD45-FITC/(CD56+CD16)-RD1/CD19-ECD/CD3-PC5 provides identification and enumeration of CD45+, CD45+ Low SS, and CD3+, CD3-/CD19+ and CD3-/CD56+CD16+ lymphocyte percentages and absolute counts in peripheral whole blood. Additionally, both panels provide for CD45+ absolute count and CD45+ Low SS absolute count and percentage.

AQUIOS Immuno-Trol and Immuno-Trol Low Cells are assayed, lysable whole blood quality control product for immunophenotyping analysis using monoclonal antibody reagents and flow cytometry. It provides a positive cell control that is processed in the same manner as a whole blood sample. This allows verification of instrument and reagent performance. It also verifies the methods used for staining targeted cells, lysing erythrocytes, and analyzing samples by the AQUIOS CL Flow Cytometer.

The AQUIOS CL Flow Cytometer uses on-board sample preparation as part of the overall system workflow. The AQUIOS Lysing Reagent Kit is comprised of two readyto-use reagents: Reagent A lyses the red blood cells, Reagent B quenches the solution, slowing the lyse reaction down in preparation for analysis. This reagent system provides a rapid, no-wash, standardized, whole blood lysing solution for sample to sample, and laboratory to laboratory reproducibility.

Here's an analysis of the acceptance criteria and study findings for the AQUIOS CL Flow Cytometry System, based on the provided document:

1. Table of Acceptance Criteria and Reported Device Performance

The document provides summary results rather than explicit, quantified acceptance criteria for many tests. However, it consistently states that the device "meets performance requirements" or "was demonstrated." Where specific performance measures or outcomes are mentioned, they are included below.

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

The document does not explicitly state the sample sizes used for the test set portion of the studies (which would typically involve independent validation after development). Instead, it describes general testing approaches. It also does not specify the country of origin for the data or whether it was retrospective or prospective.

For example, for "Method Comparison," it merely states "To evaluate bias between the subject device versus the predicate" and uses CLSI EP09-A3 (Method Comparison and Bias Estimation Using Patient Samples), which implies patient samples were used, but no quantity or demographics are given. Similarly, "Adult Reference Intervals" implies a study on adults, but sample size and demographics are not specified.

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

The document does not mention the use of experts to establish a "ground truth" for a test set in the traditional sense of image interpretation or complex diagnostic decision-making. The AQUIOS CL Flow Cytometry System is an automated cell counter. Its "ground truth" for the test set would typically be established by established reference methods, predicate devices, or validated laboratory assays (e.g., manual differential counts, confirmed cell populations by expert flow cytometrists, or validated internal methods). The document refers to "predicate devices" for comparison, which themselves are legally marketed and validated, serving as a de facto "ground truth" in terms of established performance.

4. Adjudication Method for the Test Set

Not applicable. As "ground truth" is not explicitly established by human experts in a subjective interpretation process (like in radiology), an adjudication method in the sense of resolving inter-reader disagreements is not described or implied. The system relies on comparisons to predicate devices and validated methods.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done

No. An MRMC comparative effectiveness study, which typically compares human reader performance with and without AI assistance, was not conducted. This device is an automated in vitro diagnostic system for cell counting and immunophenotyping, not a system that assists human readers in interpreting complex cases. Its "effectiveness" is measured by its analytical performance (accuracy, precision, linearity, etc.) against established laboratory methods and predicate devices.

6. If a Standalone (Algorithm Only Without Human-in-the-Loop) Performance Was Done

Yes, implicitly. The entire set of performance studies described (Fluorescence Linearity, Electronic Volume Linearity, Laser Performance, Analyzer Carryover, Instrument Settings Stability, Gravimetrics, Comparability, Assay Linearity, Assay Carryover, Detection Capability, Specimen and Prepared Sample Stability, Method Comparison, Precision, Adult Reference Intervals, Reagent Stability, Lot Variability) evaluates the device's autonomous performance. The AQUIOS CL Flow Cytometer, along with its reagents and software, is designed to perform these tasks automatically. While human operators are involved in sample preparation and loading, the core measurements and classifications are driven by the instrument's algorithms and hardware, making these standalone performance assessments. The "AQUIOS System Software" also includes algorithms for automated analysis.

7. The Type of Ground Truth Used

The ground truth for the performance studies appears to be based on:

• Comparison to predicate devices: For analytical accuracy (e.g., "Method Comparison" against FACSCalibur or UniCel DxH 800). This means the established, cleared performance of the predicate serves as the standard.
• Validated internal methods/specifications: For various instrument and assay characteristics like linearity, precision, detection limits, and stability.
• Published values: For establishing "Adult Reference Intervals," which were confirmed to be "consistent with published values for T, B, and NK lymphocyte subsets."
• CLSI (Clinical and Laboratory Standards Institute) guidelines and standards: These provide the methodological framework and often implicit performance thresholds for many tests (e.g., CLSI EP06-A for linearity, CLSI EP5-A2 for precision, CLSI H26-A2 for hematology analyzers).

8. The Sample Size for the Training Set

The document does not specify a separate "training set" or its size. For an IVD device like this, which performs quantitative measurements based on biophysical properties, the development process generally involves extensive internal testing and refinement (calibration, optimization, verification) using a wide range of samples, rather than a distinct "training set" in the machine learning sense. The performance studies described in the document are primarily for validation and verification.

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

Since a "training set" in the AI/ML context is not explicitly mentioned, the concept of establishing ground truth for it is not directly addressed. Instead, the analytical methods (flow cytometry principles, reagent chemistries, software algorithms) are based on well-established scientific principles and calibrated against reference materials and methods during the device's development and manufacturing.

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The BD FACSCanto flow cytometer (4-3-3 configuration) functions as part of a system with dedicated clinical software intended for use with cleared or approved in vitro diagnostic (IVD) assays that are indicated for use with the instrument for the identification and enumeration of human cell subsets. Only six detection channels using a blue (488 nm) and a red (640 mm) laser have been cleared for in vitro diagnostic use. For use with or without the BD FACS Sample Prep Assistant III.

For in vitro diagnostic use.

The BD FACSCanto II flow cytometers (4-2-2 and 5-3 configurations) function as part of a system with dedicated clinical software intended for use with cleared or approved in vitro diagnostic (IVD) assays that are indicated for use with the instrument for the identification and enumeration of human cell subsets. Only six detection channels using a blue (488 nm) and a red (633 mm) laser have been cleared for in vitro diagnostic use. For use with or without the BD FACS Sample Prep Assistant III.

For in vitro diagnostic use.

The BD FACSCanto and FACSCanto II (BD FACSCanto II 4-2-2, BD FACSCanto II 5-3 and BD FACSCanto 4-3-3 configurations) are comprised of a flow cytometer, a fluidics cart, and a computer workstation. The flow cytometer acquires and analyzes the sample, the fluidics cart contains operational fluids, and the computer displays and prints the analysis. The flow cytometer utilizes three subsystems: fluidics, optics, and electronics. The computer workstation runs two software packages: BD FACSCanto clinical software for automatic immunophenotyping assays prepared using the lyse/wash or lyse/no-wash methods, and BD FACSDiva software for installation, service, and manual user-validated applications. The BD FACSCanto and FACSCanto II systems can optionally be used with the BD FACSLoader for automatic sample introduction, a standalone barcode reader for data input into BD FACSCanto clinical software and BD FACSDiva software, and/or the BD FACS Sample Prep Assistant III for automatic sample preparation of assays utilizing the lyse/no-wash method.

The provided text describes a 510(k) premarket notification for the BD FACSCanto and BD FACSCanto II flow cytometers. The submission aims to demonstrate substantial equivalence to previously cleared predicate devices. The document outlines comparisons between the new configurations and the predicate devices, with emphasis on the performance of IVD (In Vitro Diagnostic) channels.

Here's an analysis of the acceptance criteria and study information:

1. Table of Acceptance Criteria and Reported Device Performance

The document does not explicitly present a table of specific numerical acceptance criteria (e.g., a required sensitivity or specificity threshold) with corresponding reported device performance values for the new configurations compared to the predicate device. Instead, it states that the new configurations demonstrated "equivalent performance to the predicate" for various studies. This "equivalent performance" implicitly serves as the acceptance criterion.

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

The document refers to "patient samples" for the Accuracy/Method Comparison study, "assay dependent" for Precision and Linearity, and "Three samples with a high White Blood Cell concentration" and "three low WBC concentration samples" for the Carryover study.

• Accuracy/Method Comparison: "patient samples" - The specific number of samples is not provided. Data provenance is not explicitly stated (e.g., country of origin, retrospective/prospective), but it is implied to be clinical samples for IVD assays.
• Precision: "Assay dependent" - Specific sample size is not provided. Data provenance is not explicitly stated.
• Linearity: "Assay- dependent" - Specific sample size is not provided. Data provenance is not explicitly stated.
• Carryover: 6 samples (3 high WBC, 3 low WBC) - Data provenance is not explicitly stated.

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 performed are instrument performance evaluations, comparing the new device configurations to the predicate device, rather than comparing to a diagnostic ground truth established by experts. The "ground truth" implicitly relies on the established performance of the predicate device.

4. Adjudication Method for the Test Set

This information is not provided in the document. Given that the studies are technical performance comparisons of the device itself rather than interpretation by human readers, an adjudication method in the context of expert review would likely not be applicable.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done, If So, What Was the Effect Size of How Much Human Readers Improve with AI vs Without AI Assistance

This document describes a flow cytometer, which is an instrument for identifying and enumerating cell subsets. It is not an AI-assisted diagnostic tool that human readers would use to interpret images or data in a comparative effectiveness study involving improving diagnostic accuracy. Therefore, an MRMC comparative effectiveness study with human readers improving with AI assistance is not applicable and was not done in this context.

6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done

The device itself is a standalone instrument (flow cytometer) with dedicated clinical software. The performance data presented (accuracy/method comparison, precision, linearity, carryover) represents the standalone performance of the instrument configurations (new vs. predicate). There is no "human-in-the-loop" aspect being evaluated in these specific performance studies, as the instrument performs the measurement and analysis for IVD assays.

7. The Type of Ground Truth Used

For the performance studies (Accuracy/Method Comparison, Precision, Linearity), the "ground truth" is effectively the performance of the legally marketed predicate device (BD FACSCanto 4-2 configuration), as the goal is to demonstrate "equivalent performance." For the Carryover study, the ground truth would be the actual concentration values and the calculated carryover, which is an intrinsic characteristic of the instrument's fluidics and detection system.

8. The Sample Size for the Training Set

This information is not provided. The document describes new configurations of an existing flow cytometer system and its software, demonstrating substantial equivalence to a predicate device. It does not mention machine learning or AI models undergoing a 'training' phase in the traditional sense, for which a training set size would be relevant. The software performs automated immunophenotyping based on established algorithms rather than adaptive learning from a dataset.

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

Since a "training set" in the context of machine learning is not mentioned as part of this submission, the method for establishing its ground truth is not applicable/not provided. The software algorithms integral to the device's function are based on engineering design and validation, not on a machine learning training paradigm.

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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 letraCHROME CD45-FITC/CD4-RD1/CD8-ECD/CD3-PC5 and CYTO-STAT terrCHROME CD45-FITC/CD56-F • C Y (O-S FAT TetraCHKOME CD4-FFTCCO4+KD7/CDV-Fc2/CD3 P ovide identification and numeration of CD3+CD4+CD4+CD4+CD4+CD4+ KDI/CDI9-ECD/CD3+CS monocolal antibody reagains. There reges and absolute counts in peripleral whole blood. Absolute method) CD3+CD8+, CD3+, CD19+ and CD3-CD3+ Tymphoeyto percomes (single platform lections of the may be in closing acrescription of parient counts may be celermined by the Navio Cyclinece asng I to "Outlier" (o" on the in the immunologic assessment of patients having or suspected of having immune deficiency.
• Navios tetra Software for automated and results with CYTO-STAT terraCHRONE CD45-FFTC/CD4-RD/VCD8-ECD/CD3-FCD/CD3-• Navios letta Soltware for adionated and results will of 10 0 010 11:40 pm
PC5 and CYTO-STAT ietraCHROME CD45 FITC/CD56-RDI/CD19-ECD/CD3-PCS monoclonal antibody reagents.
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Navios Software may be installed on an independent computer workstarion for off issues of listed of line against must he Navios Soltware may be installed on the incependent compaise frectorial and software package listed above. The off-line analysis must be performed in accordance with the product labeling.

The Navios tetra Software is intended for use as an in vitro diagnostic device for immunophenoyping with CYTC/CDS6 RD/A The Navios tera Software is mielided to use as an in Thir Glightshouse on minutes of the Subsition of the National Provincial Provinces of CD19-FITC/CD56-RDI/CD19-ECV/ CD3-PC5 monoclonal antibody reagents on the Navios Flow Cytometer.
It provides automated analysis and results for the identification and enumeration of CD3+CD4+, CD19+, CD19+, and If provides and results for the nemation and while blood. Absolute counts may be determined by the except of the CD3+CD5+ iymphocyte percentages and alsolute counts in perfined in separate hematology results (dual Navios now cycomerer use in the immunologic assessment of patients having or suspected of having immune deficiency.
platform method). It is indicated for use in the immunolog

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 and Navios Flow Cytometers.

The Navios Flow Cytometer system is composed of the following components:

• Navios Flow Cytometer .
• Navios tetra Software .
• Navios Software (off-line analysis tool) .
• Flow-Set Pro Fluorospheres .
• CYTO-STAT teiraCHROME reagents .
• COULTER IMMUNOPREP Reagent System .
• TQ-Prep Workstation (Accessory for Sample Preparation) .
• PrepPlus™ 2 Workstation (Accessory for Sample Preparation) .

The Navios Flow Cytometer uses flow cytometric principles to determine qualitative and quantitative measurements of biological and physical properties of cells and other particles. These properties are measured when the cells pass through the laser beam(s) in single file.

The Navios tetra software is an optional locked algorithm application plug-in that is designed for the Navios flow cytometer. It provides automated analysis and results for tetraCHROME reagents; this application cannot be modified by the user.

The Navios Flow Cytometry System also offers an optional standalone offline software package, Navios software, which may be installed on an independent computer workstation for off-line analysis of listmode files generated by the Navios Flow Cytometer with tetraCHROME reagents and Navios tetra software according to the product labeling.

tetraCHROME CD45-FITC/CD4-RD1/CD8-ECD/CD3-PC5 CYTO-STAT reagent provides identification and enumeration of CD3+CD4+, CD3+CD8+, and CD3+ lymphocyte percentages and absolute counts in peripheral whole blood. CYTO-STAT tetraCHROME CD45-FITC/CD56-RD1/CD19-ECD/CD3-PC5 reagent provides identification and enumeration of CD3+, CD19+ and CD3-CD56+ lymphocyte percentages and absolute counts in peripheral whole blood.

Flow-Set Pro Fluorospheres is a suspension of fluorospheres with uniform and stable size and fluorescence intensity. The stability of these product parameters allows for the standardization of light scatter and fluorescence intensity instrument settings.

The COULTER ImmunoPrep Reagent System is comprised of 3 ready-to-use reagents: Reagent A lyses the red blood cells, Reagent B buffers the solution and stops the lysing process, and Reagent C fixes the cells. This reagent system provides a rapid, no-wash, standardized, whole blood lysing solution for sample to sample, and laboratory to laboratory reproducibility.

The Navios Flow Cytometer uses sample preparation devices as part of the overall workflow system. The COULTER TQ-Prep Workstation is used with the COULTER ImmunoPrep Reagent System to prepare leukocytes from whole blood for quantitative immunofluorescence measurements on flow cytometers. The COULTER PrepPlus 2 is a microprocessor-controlled pipetting and diluting system, designed for automating sample preparation or assay methods. It is capable of aspirating and dispensing liquid samples.

Here's a breakdown of the acceptance criteria and study information for the Navios Flow Cytometer System, based on the provided text.

Acceptance Criteria and Device Performance

The submission details several studies conducted to demonstrate the performance of the Navios Flow Cytometer system. The "Study Results" column in the table below directly indicates if the device met acceptable results for the respective criteria.

Study Information

The document is a 510(k) summary, which typically provides a high-level overview of validation studies rather than detailed protocols. As such, some specific details like exact sample sizes for training/test sets, data provenance, and expert qualifications are not explicitly stated in the provided text.

1. Sample Sized used for the test set and the data provenance (e.g. country of origin of the data, retrospective or prospective)

• Sample Size for Test Set: Not explicitly stated in the provided text. The "Accuracy" study mentions using "Patient Samples" based on CLSI EP9-A2. The "Precision" study used "Whole Blood Repeatability." The "Manual Pipette vs. PrepPlus 2 Method Comparison" also used "specimens." However, the exact number of samples or patients for any of these studies is not provided.
• Data Provenance: Not explicitly stated (e.g., country of origin). The studies appear to be prospective validation studies conducted by the manufacturer, Beckman Coulter, Inc.

2. Number of experts used to establish the ground truth for the test set and the qualifications of those experts (e.g. radiologist with 10 years of experience)

• Not explicitly stated. Given that the device is an "Automated Differential Cell Counter" for immunophenotyping, the ground truth would likely be established through a recognized reference method performed by trained laboratory personnel on an established, validated system. The document compares performance to a predicate device (Cytomics FC 500 with tetraCXP software), implying that the predicate's results served as a comparative "ground truth" or reference.

3. Adjudication method (e.g. 2+1, 3+1, none) for the test set

• Not explicitly stated. Adjudication methods are typically relevant for subjective interpretations (e.g., image analysis by multiple radiologists). For quantitative measurements from a flow cytometer, the ground truth is usually derived from a reference method with inherent analytical precision, rather than adjudicated expert opinions.

4. If a multi reader multi case (MRMC) comparative effectiveness study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance

• No, an MRMC comparative effectiveness study was not done in the context of human readers improving with AI assistance. The Navios system is an automated flow cytometer with software for automated analysis (Navios tetra software). The comparisons are between the new device and a predicate device (another automated system), and between different methods on the same device (e.g., single vs. dual platform absolute counting) or different sample preparation methods. This is not a human-in-the-loop AI system where human reader performance would be the primary metric.

5. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done

• Yes, standalone performance was assessed. The entire suite of performance studies (Accuracy, Precision, Linearity, Carryover, Limits, etc.) for the Navios Flow Cytometer and its associated Navios tetra software (which is an "optional locked algorithm application plug-in that is designed for the Navios flow cytometer. It provides automated analysis and results") represent standalone algorithm performance. The device is intended "for automated analysis and results."

6. The type of ground truth used (expert concensus, pathology, outcomes data, etc)

• The ground truth for the analytical performance studies (Accuracy, Precision, Linearity, etc.) appears to be based on:
  • Comparison to a predicate device: The accuracy study directly states "comparable results to the predicate device." The predicate device (Cytomics FC 500 with tetraCXP software) represents an established and accepted method for immunophenotyping.
  • Established analytical methods and guidelines: Studies refer to CLSI (Clinical and Laboratory Standards Institute) guidelines (e.g., CLSI EP9-A2 for Method Comparison, CLSI EP5-A2 for Precision, CLSI EP06-A for Linearity). These guidelines define methods to establish the true analytical performance characteristics of a quantitative diagnostic device, implicitly establishing a "true value" or "ground truth" to compare against.
  • Reference Intervals: Reference intervals were established for the device, which involves testing healthy populations to define normal ranges.

7. The sample size for the training set

• Not explicitly stated. The document describes performance studies, which are typically conducted on independent test sets after an algorithm has been developed and trained. Information about specific training set sizes used to develop the "Navios tetra software" algorithm is not provided in this regulatory summary.

8. How the ground truth for the training set was established

• Not explicitly stated. As this is a 510(k) summary focused on post-development performance validation, details on the training process and ground truth establishment for the development phase of the "Navios tetra software" algorithm are not included. Generally, for such systems, training data would be meticulously characterized using established laboratory methods or reference instruments, with expert review to ensure accuracy of the labels.

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tetraCHROME Reagents:
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 and Cytomics FC 500 Flow Cytometers. The reagents may also be used with the tetraONE SYSTEM for COULTER EPICS XL/XL-MCL Flow Cytometers or with tetraCXP SYSTEM for Cytomics FC 500 Flow Cytometers.

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 CD4+, 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.

tetraCXP SYSTEM:
The tetraCXP Software for Cytomics FC 500 flow cytometry systems, CYTO-STAT tetraCHROME CD45-FITC/CD4-RD1/CD8-ECD/CD3-PC5, and CYTO-STAT tetraCHROME CD45-FITC/CD56-RDI/CD19-ECD/CD3-PC5 Monoclonal Antibody Reagents combine four-color fluorescent monoclonal antibody reagents, quality control reagents, an optional absolute count reagent, and software for automated analysis of lymphocyte populations in whole blood using Cytomics FC 500 flow cytometry systems with CXP Software.

The system with CYTO-STAT tetraCHROME CD45-FITC/CD4-RD1/CD8-ECD/CD3-PC5 is intended "For In Vitro Diagnostic Use" and allows simultaneous identification and enumeration of total CD3+, total CD4+, total CD8+, dual CD3+/CD4+ and dual CD3+/CD8+ T lymphocyte population percentages and absolute counts. The system also provides the CD4/CD8 ratio.

The system with CYTO-STAT tetraCHROME CD45-FITC/CD56-RD1/CD19-ECD/CD3-PC5 is intended "For In Vitro Diagnostic Use" and allows simultaneous identification and enumeration of total CD3+ (T), CD19+(B), and CD3-/CD56+ (NK) lymphocyte population percentages and absolute counts. This reagent reflects the distribution of the three major subsets comprising the lymphocyte population upon which other lymphocyte enumeration studies are based.

CYTO-STAT tetraCHROME CD45-FITC/CD4-RD1/CD8-ECD/CD3-PC5 Monoclonal Antibody Reagent: This monoclonal antibody reagent identifies a lymphocyte gate based on CD45 bright positive staining (vs. side scatter) and allows simultaneous identification and enumeration of total CD3+, total CD4+ total CD8+, dual-positive CD3+/CD4+ and dual-positive CD3+/CD8+ lymphocytes in whole blood by flow cytometry. The reagent is comprised of four murine monoclonal antibodies. Each antibody is labeled with a different color fluorochrome. The reagent is for use on the COULTER EPICS XL/XL-MCL and Cytomics FC 500 Flow Cytometers with a manual gating procedure provided in the reagent product labeling. The reagent may also be used with the automated algorithm gating provided by tetraONE SYSTEM for COULTER EPICS XL/XL-MCL Flow Cytometers or tetraCXP SYSTEM for Cytomics FC 500 Flow Cytometers.

CYTO-STAT tetraCHROME CD45-FITC/CD56-RD1/CD19-ECD/CD3-PC5 Monoclonal Antibody Reagent: This monoclonal antibody reagent identifies a lymphocyte gate based on CD45 bright positive staining (vs. side scatter) and allows simultaneous identification and enumeration of total CD3+, CD19+ and CD3-/CD56+ lymphocytes in whole blood by flow cytometry. The reagent is comprised of four murine monoclonal antibodies. Each antibody is labeled with a different color fluorochrome. The reagent is for use on the COULTER EPICS XL/XL-MCL and Cytomics FC 500 Flow Cytometers with a manual gating procedure provided in the reagent product labeling. The reagent may also be used with the automated algorithm gating provided by tetraONE SYSTEM for COULTER EPICS XL/XL-MCL Flow Cytometers or tetraCXP SYSTEM for Cytomics FC 500 Flow Cytometers.

tetraCXP SYSTEM: tetraCXP SYSTEM for the Cytomics FC 500 with CXP Software consists of tetraCXP SYSTEM application software, tetraCHROME monoclonal antibody reagents, quality control reagents, an optional absolute count reagent, and automated software on the Cytomics FC 500 Flow Cytometer. The system with CYTO-STAT tetraCHROME CD45-FITC/CD4-RD1/CD8-ECD/CD3-PC5 allows for simultaneous identification and enumeration of total CD3+, total CD4+, total CD8+, dual CD3+/CD4+ and dual CD3+/CD8+ T lymphocyte population percentages and absolute counts. The system also provides the CD4/CD8 ratio. The system with CYTO-STAT tetraCHROME CD45-FITC/CD56-RD1/CD19-ECD/CD3-PC5 is intended "For In Vitro Diagnostic Use" and allows simultaneous identification and enumeration of total CD3+ (T), CD19+ (B), and CD3-/CD56+ (NK) lymphocyte population percentages and absolute counts. The tetraCXP SYSTEM Software comprises two functions: an Auto-Set Panel and an Automated Analysis Algorithm. The Auto-Set Panel automatically standardizes the cytometer, adjusts compensation settings, passes cytometer settings to designated test protocols, and verifies cytometer setup and antibody performance. Compensation settings are determined using QuickCOMP 4 Cells. The Automated Analysis Algorithm works in conjunction with the tetraCHROME monoclonal antibodies to automatically identify and enumerate sample populations.

Here's a breakdown of the acceptance criteria and study information for the Beckman Coulter CYTO-STAT® tetraCHROME™ reagents and tetraCXP SYSTEM, based on the provided document K121445:

1. Table of Acceptance Criteria and Reported Device Performance

The provided document describes a Special 510(k) submission for changes related to labeling claims for specimen and prepared sample stability. The specific acceptance criteria themselves are not explicitly detailed in the document. Instead, the study results simply state that these criteria were met.

Therefore, I will present the acceptance criteria based on what the study aimed to demonstrate (stability limits) and the reported performance as a confirmation of meeting those (unspecified) limits.

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

• Sample Size for Test Set: The document does not specify the sample size used for the stability studies. It only mentions "Specimens tested at various time intervals."
• Data Provenance: The document does not specify the country of origin of the data or whether the study was retrospective or prospective.

3. Number of Experts Used to Establish Ground Truth and Their Qualifications

This type of study (stability testing of flow cytometry reagents and system) does not typically involve human experts establishing "ground truth" in the same way, for example, a diagnostic imaging study would. The ground truth here is inherently defined by the physical stability of the biological samples and the accurate measurement capabilities of the flow cytometer and its software.

Therefore, the concepts of "number of experts" and "qualifications of those experts" for establishing ground truth are not applicable in this context. The "ground truth" would be established by the validated methods of measuring cell populations over time, using predicate devices or established laboratory techniques as a reference.

4. Adjudication Method for the Test Set

Since human expert assessment and "ground truth" in the interpretive sense are not relevant for this type of stability study, an adjudication method is not applicable. The results are quantitative measurements from a machine and are assessed against predefined performance metrics.

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

A Multi-Reader Multi-Case (MRMC) comparative effectiveness study was not performed for this submission. This type of study is typically relevant for evaluating the impact of an AI system on human interpretive performance, which is not the subject of this 510(k) special submission. The submission focuses on the stability of specimens and prepared samples when used with the reagents and system.

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

The tetraCXP SYSTEM with its Automated Analysis Algorithm does operate in a "standalone" fashion for identifying and enumerating cell populations. The submission states: "The Automated Analysis Algorithm works in conjunction with the tetraCHROME monoclonal antibodies to automatically identify and enumerate sample populations."

However, the specific "study that proves the device meets the acceptance criteria" in this Special 510(k) is about specimen and prepared sample stability when used with the system. While the system has an automated algorithm, this submission is not presenting new standalone performance data for the algorithm itself, but rather validating the stability claims. The original performance of the automated algorithm was cleared under predicate devices (K030828 for the tetraCXP SYSTEM).

7. Type of Ground Truth Used

For the stability studies, the "ground truth" would have been established by performing measurements at baseline (Time 0) and then comparing subsequent measurements at various time intervals to these baseline values. The "ground truth" for the cell population enumeration itself (CD3+, CD4+, etc.) is based on the known specific binding of the monoclonal antibodies to their respective antigens and the accurate detection by the flow cytometer, often correlated with established manual gating procedures or validated reference methods.

In essence, the ground truth for stability is the initial measurement, and the acceptance criteria define the allowable deviation from this initial measurement over time.

8. Sample Size for the Training Set

This submission is a Special 510(k) for changes to labeling claims regarding sample stability, not for the development or re-evaluation of the automated analysis algorithm itself. Therefore, information regarding the sample size for the training set for the tetraCXP SYSTEM's algorithm is not provided in this document. This data would have been part of the original 510(k) submission for the tetraCXP SYSTEM (K030828).

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

Similar to point 8, this information pertains to the original development of the tetraCXP SYSTEM's automated algorithm, not this specific Special 510(k) submission. Therefore, the document does not provide details on how the ground truth for the training set of the automated algorithm was established. It is highly probable that the ground truth for algorithm training would have involved expert-gated flow cytometry data serving as the reference for various lymphocyte populations observed.

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