(84 days)
The tetraONE™ SYSTEM for EPICS® XL™ Flow Cytometry Systems with CYTO-STAT® tetraCHROME™ CD45-FITC/CD4-RD1/CD8-ECD/CD3-PC5 Monoclonal Antibody Reagent and CYTO-STAT® tetraCHROME™ CD45-FITC/CD56-RD1/CD19-ECD/CD3-PC5 Monoclonal Antibody Reagent 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 EPICS® XL™ flow cytometry systems with SYSTEM II™ Software. The system is intended "For In Vitro Diagnostic Use" and allows simultaneous identification and enumeration of total CD3+, total CD4+, total CD8+, dual CD3+/CD4+, dual CD3+/CD8+, CD19+, and CD3-/CD56+ lymphocyte population percentages and absolute counts. The system also provides the T4/T8 ratio when using CYTO-STAT® tetraCHROME™ CD45-FITC/CD4-RD1/CD8-ECD/CD3-PC5 Monoclonal Antibody Reagent, and total lymphocyte percentage when using CYTO-STAT® tetraCHROME™ CD45-FITC/CD56-RD1/CD19-ECD/CD3-PC5 Monoclonal Antibody Reagent.
CD3+, CD4+, CD8+, and/or CD19+ lymphocyte percentages and absolute counts may be used as aids to evaluate immune competency underlying known or unknown disease states and to monitor lymphocyte levels following organ transplantation.
To illustrate, identification of abnormal levels of CD3+, CD4+, CD8+, and/or CD19+ lymphocytes may aid in the diagnosis and/or prognosis of unidentified disease conditions in patients with altered white blood cell counts. Altered percentages of CD3+, CD4+, CD8+, and/or CD19+ lymphocytes recorded following organ (for example, kidney, heart, liver, lung) transplantation suggests T (CD3+, CD4+, CD8+) and/or B (CD19+) lymphocyte measurements may be useful as aids in monitoring these cellular populations.
Identification of abnormal levels of CD4+ immunodeficiency might also aid in the diagnosis of immunodeficiency disease. For example, infection with human immunodeficiency virus (HIV), the etiologic agent of acquired immunodeficiency syndrome (AIDS), results in profound immunosuppression due predominantly to a selective of the CD4+ lymphocytes that express the receptor for the virus, which is associated with the CD4+ antigen. Progressive clinical and immunologic deterioration generally correlated with a falling CD4+ lymphocyte count.
NK (Natural Killer) lymphocyte populations have been functionally defined as a lymphocyte population capable of mediating non-MHC restricted cytotoxicity against targets such as certain tumor and virus-infected cells.
CYTO-STAT® tetraCHROME™ CD45-FITC/CD56-RD1/CD19-ECD/CD3-PC5 provides the ability to comprehensively identify and enumerate an individual's major lymphocyte subsets: T, B and NK. Used as a four color Lymphocyte Immunophenotyping Panel, CYTO-STAT® tetraCHROME™ CD45-FITC/CD4-RD1/CD8-ECD/CD3-PC5 and CYTO-STAT® tetraCHROME™ CD45-FITC/CD56-RD1/CD19-ECD/CD3-PC5 also function as a quality control check for a specimen in terms of CD3+ lymphocyte measurement reproducibility within the Panel.
The tetraONE™ SYSTEM for EPICS® XL™ Flow Cytometry Systems with CYTO-STAT® tetraCHROME™ CD45-FITC/CD4-RD1/CD8-ECD/CD3-PC5 Monoclonal Antibody Reagent and CYTO-STAT® tetraCHROME™ CD45-FITC/CD56-RD1/CD19-ECD/CD3-PC5 Monoclonal Antibody Reagent 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 EPICS® XL™ flow cytometry systems with SYSTEM II™ Software.
Here's a breakdown of the acceptance criteria and study information for the tetraONE™ SYSTEM, based on the provided text:
1. Table of Acceptance Criteria and Reported Device Performance
The document describes the performance specifications for the CYTO-STAT® tetraCHROME™ CD45-FITC/CD56-RD1/CD19-ECD/CD3-PC5 reagent within the tetraONE™ SYSTEM. While explicit numerical acceptance criteria (e.g., minimum correlation coefficient, maximum CV) are not quantified directly in the provided text as a specific table of acceptance criteria, the study design and results implicitly indicate the performance levels deemed acceptable for each tested parameter.
| Performance Characteristic | Acceptance Criteria (Implicit from Study Design/Conclusion) | Reported Device Performance (Summary from Study) |
|---|---|---|
| Accuracy | Comparison to predicate devices (CD3/B4 and CD3/CD56) with "essentially identical" results for identifying and enumerating targeted lymphocytes. | "Results analyzed in terms of minimums, means ± 1 SD, confidence intervals, regression analyses and analyses of variance demonstrated that CD45/CD56/CD19/CD3, CD3/CD56 identify and enumerate essentially identical numbers of the targeted lymphocytes in whole blood specimens." |
| Linearity | Demonstration of linearity between recovered and expected absolute counts across a range of lymphocyte concentrations. | "Results analyzed in terms of regression and correlation analyses for recovered versus expected absolute count demonstrated Linearity of the assay." |
| Precision (Within Run/Intralaboratory) | Demonstration of acceptable mean, standard deviation (SD), and Coefficient of Variation (CV) for replicate measurements at various lymphocyte concentrations. | "Results analyzed in terms of mean ± 1 SD and CV demonstrated Within Run (Intralaboratory) Precision of the assay." |
| Precision (Interlaboratory) | Demonstration of acceptable mean, standard deviation (SD), and Coefficient of Variation (CV) for replicate measurements across different laboratories. | "Results analyzed in terms of mean ± 1 SD and CV demonstrated Interlaboratory Precision of the assay." |
2. Sample Sizes Used for the Test Set and Data Provenance
- Test Set Sample Size:
- Accuracy: "Normal and abnormal whole blood specimens were collected from geographically diverse populations of males and females unselected as to race and ranging in age from 18 to 84 years." The specific number of specimens is not provided in the text.
- Linearity: Not specified, but involved a "concentrated COULTER™ CYTO-TROL™ Control Cells sample serially diluted" to achieve a range of concentrations.
- Precision (Within Run): "Ten replicate measurements were made for each of three levels of CD3+, CD19+ and CD3-/CD56+ lymphocyte concentrations." The number of individual patient samples used to create these 'levels' is not specified.
- Precision (Interlaboratory): "Ten replicate measurements were made on the same day using different laboratories... All measurements were made on a single normal whole blood specimen". The number of laboratories is not specified.
- Data Provenance: The specimens for the Accuracy study were "collected from geographically diverse populations." This suggests it was retrospective for the purpose of the study (pre-collected as "specimens") and likely from the USA given the company and regulatory body location, though "geographically diverse" could imply wider sourcing. Linearity and Precision studies used control cells or single normal whole blood specimens, which are laboratory-prepared or sourced.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Their Qualifications
- Not Applicable. This device is a diagnostic reagent system for flow cytometry, not an AI or imaging device that requires human expert interpretation for ground truth. The "ground truth" for this type of device is established by the performance of the predicate device and objective measures like cell counts, percentages, and statistical comparisons, rather than expert consensus on interpretive tasks.
4. Adjudication Method (for the test set)
- Not Applicable. As mentioned above, this study does not involve subjective interpretations requiring adjudication. Performance is assessed through statistical analysis against predicate devices and known analytical characteristics (linearity, precision).
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was done
- No. An MRMC study is not relevant for this type of in vitro diagnostic device, which evaluates the analytical performance of a reagent system rather than human reader accuracy with or without AI assistance.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) was done
- Yes, effectively. The entire study described assesses the performance of the tetraONE™ SYSTEM (reagents and software for automated analysis) in a standalone analytical context. Human involvement is in operating the flow cytometer and processing samples, but the "performance" being evaluated is that of the system itself in identifying and enumerating cell populations, not a human interpretation task. The results (cell counts, percentages) are direct outputs of the system, compared against predicate systems.
7. The Type of Ground Truth Used
- The ground truth used is effectively predicate device performance and analytical correctness (e.g., expected values from diluted control cells, consistency in replicate measurements). For accuracy, the new device's results (CD45/CD56/CD19/CD3) were compared against established predicate devices (CD3/B4 and CD3/CD56) which are presumably considered the "gold standard" or accepted method for enumerating these lymphocyte populations. For linearity and precision, the ground truth is the expected performance based on known dilutions or statistical characteristics of repeated measurements.
8. The Sample Size for the Training Set
- Not Applicable/Not Specified. This document describes the validation of an in vitro diagnostic reagent and software system, not an AI model that undergoes a distinct "training" phase with a large dataset in the conventional machine learning sense. The software's algorithms for automated analysis are likely based on established flow cytometry principles and, while potentially "developed" using data, the document does not refer to a specific "training set" in the context of deep learning or similar AI models.
9. How the Ground Truth for the Training Set was Established
- Not Applicable. (See point 8). The "ground truth" for the development of such an IVD system's algorithms would typically be based on established immunological principles, manual gating by expert flow cytometrists, and historical data from previous generations of flow cytometry systems, rather than a separate, explicitly defined "training set ground truth" as understood in modern AI development.
§ 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.”