FDA 510(k) Search - By Innolitics (SaMD and AI Experts)

The tetraONE™ SYSTEM for EPICS® XL Flow Cytometry Systems and CYTO-STAT® tetraCHROME™ CD45-FITC/CD4-RD1/CD8-ECD/CD3-PC5 Monoclonal Antibody Reagent combines a four-color fluorescent monoclonal antibody reagent, four quality control reagents, an optional absolute count reagent, and software for automated analysis of lymphocyte populations in whole blood using EPICS® XL Flow Cytometry Systems with SYSTEM II™ Software. The tetraONE™ SYSTEM software is designed to further simplify flow cytometric analysis by increasing automated modes of operation and the accuracy, precision and reliability of results. The tetraONE™ SYSTEM does not require an isotypic control for monitoring and adjusting for non-specific and nontargeted monoclonal antibody binding to irrelevant cellular populations. The tetraONE™ SYSTEM software monitors and adjusts for such binding by automatically placing cursors based on the separation of positive and negative peaks. The CD45/CD4/CD3 reagent contains a monoclonal antibody, CD45, to identify a lymphocyte gate to allow CD3+, CD4+, CD8+, dual-positive CD3+/CD4+ and dualpositive CD3+/CD8+ measurements.

AI/ML Overview

The acceptance criteria and study proving the device meets them are summarized below:

Acceptance Criteria and Reported Device Performance

Acceptance Criteria	Reported Device Performance
Accuracy: CD3+, CD4+, CD8+, CD3+/CD4+ and CD3+/CD8+ percentages and absolute counts comparable to predicate devices (CD3/T4 and CD3/T8).	Results from comparison with CD3/T4 and CD3/T8 demonstrated that CD45/CD4/CD8/CD3, CD3/T4, and CD3/T8 identify and enumerate essentially identical numbers of targeted lymphocytes in whole blood specimens. Analysis included minimums, maximums, means ± 1 SD, 95% confidence intervals, regression and correlation analyses, and analyses of variance.
Linearity: The assay should demonstrate linearity over a range of lymphocyte concentrations.	Regression and correlation analyses for recovered versus expected absolute counts demonstrated linearity of the assay.
Within Run (Intralaboratory) Precision: Consistent measurements for lymphocyte concentrations within single laboratory runs.	Results for mean ± 1 SD and CV demonstrated Within Run (Intralaboratory) Precision of the assay.
Interlaboratory Precision: Consistent measurements for lymphocyte concentrations across different laboratories.	Results for mean ± 1 SD and CV demonstrated Interlaboratory Precision of the assay.

Study Information

Sample sizes used for the test set and the data provenance:
- Accuracy: Normal and abnormal (e.g., Human Immunodeficiency Virus, organ transplant, autoimmune disease, low white blood cell count) whole blood specimens. The exact number of specimens is not specified, but they were collected from "geographically diverse populations of males and females unselected as to race and ranging in age from 18 to 85 years."
- Linearity: One concentrated COULTER™ CYTO-TROL™ Control Cells sample, serially diluted to achieve a range of CD3+, CD4+ (CD3+/CD4+), and CD8+ (CD3+/CD8+) lymphocyte concentrations. Three replicate measurements were made.
- Within Run (Intralaboratory) Precision: A normal whole blood specimen selectively depleted to create three levels of CD3+, CD4+ (CD3+/CD4+), and CD8+ (CD3+/CD8+) lymphocyte concentrations. Ten replicate measurements were made for each level.
- Interlaboratory Precision: A single normal whole blood specimen. Ten replicate measurements were made on the same day using different laboratories and EPICS® XL-MCL flow cytometers.
- Data Provenance: Not explicitly stated, but "geographically diverse populations" and the mention of "COULTER CORPORATION
  P.O. BOX 169015
  Miami, Florida 33116-9015 USA" and various international branches suggest data could be from multiple locations, but specific countries are not detailed. All studies appear to be prospective to assess the performance of the new device.
Number of experts used to establish the ground truth for the test set and the qualifications of those experts: Not applicable. The ground truth for this device (a lymphocyte immunophenotyping system) is established through comparison with existing, well-validated methods (CD3/T4 and CD3/T8 reagents) and control materials (COULTER™ CYTO-TROL™ Control Cells). The assessment relies on the measurements obtained from these established methods and the inherent properties of the control cells, rather than expert consensus on individual specimens.
Adjudication method for the test set: Not applicable. The study involves direct comparison of measurements between the new device and established methods, or assessment against known concentrations (linearity) and variability (precision). There is no mention of human adjudication of results in the traditional sense.
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: Not applicable. This is a medical device for automated laboratory analysis (flow cytometry) and does not involve human readers interpreting images or data that an AI would assist with. The "software for automated analysis" refers to process automation, not AI-assisted human interpretation.
If a standalone (i.e. algorithm only without human-in-the-loop performance) was done: Yes. The device, the tetraONE™ SYSTEM, including its software, performs automated analysis. The studies described are evaluating the performance of this system directly, without human intervention during the measurement and analysis process beyond setting up the experiment and operating the flow cytometer. The software "is designed to further simplify flow cytometric analysis by increasing automated modes of operation and the accuracy, precision and reliability of results." The system "automatically placing cursors based on the separation of positive and negative peaks."
The type of ground truth used:
- Accuracy: The "ground truth" for accuracy was established by comparing the measurements from the new tetraONE™ SYSTEM with those obtained using predicate devices (CYTO-STAT®/COULTER CLONE® CD3(IgG1)-FITC/T4-RD1 and CD3(IgG1)-FITC/T8-RD1 Monoclonal Antibody Reagents), which are considered established and reliable methods for lymphocyte immunophenotyping. Lymphocyte purity corrections were applied to the comparator values.
- Linearity: The ground truth was based on expected concentrations from serially diluted control cell samples (COULTER™ CYTO-TROL™ Control Cells), implying known or reliably characterized target concentrations.
- Precision: The ground truth for precision was the measured concentrations themselves across multiple replicates, evaluated for consistency rather than absolute accuracy against an external standard.
The sample size for the training set: Not explicitly stated. The document describes product testing (validation) for the device, not the development or training of its internal models. Any development/training samples used for the software's automated analysis capabilities would likely have been part of an earlier phase of product development, not detailed in this premarket notification.
How the ground truth for the training set was established: Not explicitly stated as the document focuses on product testing/validation rather than the software development process. However, given the nature of flow cytometry and the comparison with predicate devices, it can be inferred that ground truth for any potential "training" (e.g., for automated cursor placement) would have been established through well-characterized samples, potentially validated by expert review of plots and comparison to established methods over time.

Summary

Regulation Number and Section

§ 864.5220 Automated differential cell counter.

(a)
Identification. An automated differential cell counter is a device used to identify one or more of the formed elements of the blood. The device may also have the capability to flag, count, or classify immature or abnormal hematopoietic cells of the blood, bone marrow, or other body fluids. These devices may combine an electronic particle counting method, optical method, or a flow cytometric method utilizing monoclonal CD (cluster designation) markers. The device includes accessory CD markers.(b)
Classification. Class II (special controls). The special control for this device is the FDA document entitled “Class II Special Controls Guidance Document: Premarket Notifications for Automated Differential Cell Counters for Immature or Abnormal Blood Cells; Final Guidance for Industry and FDA.”