(360 days)
The Cito CBC system is a quantitative automated hematology analyzer intended for in-vitro diagnostic use to determine the following parameters with whole blood anticoagulated with K2EDTA (Venous):
-
CBC parameters: white blood cell count (WBC), red blood cell count (RBC), platelet count (PLT), hemoglobin concentration (HGB), hematocrit (HCT), and mean corpuscular volume (MCV);
-
5-Part WBC Differential (WBC Diff): neutrophil count and percentage (NEUT and NEUT%), lymphocyte count and percentage (LYMPH and LYMPH%), monocyte count and percentage (MONO and MONO%), eosinophil count and percentage (EO and EO%), basophil count and percentage (BASO and BASO%).
It is not indicated for use in diagnosing or monitoring of oncology patients, critically ill patients, or children under the age of 2 years.
The Cito CBC system is an automated hematology analyzer that is intended to analyze human whole blood, and report results of 16 hematology parameters. The system consists of a tabletop analyzer, the Cito CBC Analyzer, and a disposable test cartridge, the Cito CBC Cartridge. The analyzer includes software with Graphic User Interface to guide users to complete test procedure. To perform a test, the test cartridges and other test consumables are provided as a test kit. The current version of the test cartridge is designed for testing whole blood anticoagulated with K2EDTA. The current version of the test kit is designed for testing venous whole blood collected in a vacutainer tube.
The Cito CBC analyzer utilizes the principle of fluorescent flow cytometry for cell count and cell classification. A laser is used as the light source, and fluorescence and light scattering signals are detected for the measurements. For fluorescent labeling, blood cells are treated with a fluorescent dye that has high affinity binding to nucleic acid. Additionally, the analyzer utilizes the principle of two-wavelength photometry for the measurement of hemoglobin. Blood cells are lysed to release hemoglobin. Meanwhile, the light scattering signal measured from the flow cytometry and the light absorption signals measured from the photometry are both used to quantify the hematocrit and the mean corpuscular volume.
The Cito CBC cartridge is self-contained with all reagents to perform a test. The blood sample is applied to the test cartridge, and the test cartridge is inserted into the analyzer to complete the test. The analyzer has a pneumatic module which provides pressure to the cartridge and drives the applied sample to mix with reagents to form multiple sample mixtures. The cartridge has transparent flow cells to support the measurements of sample mixtures by fluorescent flow cytometry and photometry. The sample mixtures and the measurement wastes are all self-contained inside the cartridge for safe disposal after the test.
The CytoChip Inc. Cito CBC System (K240402) is an automated hematology analyzer intended for in-vitro diagnostic use to determine various complete blood count (CBC) and 5-part white blood cell (WBC) differential parameters. The device is not indicated for use in diagnosing oncology patients, critically ill patients, or children under the age of 2 years.
Here's a breakdown of the acceptance criteria and the studies conducted to prove the device meets these criteria:
1. Table of Acceptance Criteria and Reported Device Performance
The provided document details various studies with stated acceptance criteria, although the specific numerical targets for each parameter's acceptance criteria are not explicitly presented in a consolidated table format. Instead, the document generally states that "met the acceptance criteria" for each study. However, the outcomes demonstrating successful adherence to these criteria are reported.
Here's a summary derived from the document:
| Study Type | Acceptance Criteria (General) | Reported Device Performance (Outcome) |
|---|---|---|
| Precision-Repeatability | Pooled StDev and %CV within specified limits across low, normal, and high intervals. | Met the acceptance criteria for all reported parameters in the three intervals and at the medical decision levels. |
| Reproducibility (QC Material) | Total %CV/StDev within specified limits for each control level. | Total %CV/StDev of reported parameters for each of the three levels all met the acceptance criteria. |
| Linearity | Percentage bias thresholds defined for each parameter for linear range. | Established the linearity intervals of the reported parameters; implicitly met criteria based on "established." |
| Detection Limit (LoQ) | LoQ determined individually for cartridge lots. | LoQ for each parameter was determined; implicitly met criteria based on "determined." |
| Assay Measuring Range | Defined based on linearity and LoQ. | Established by combining linearity and LoQ results, implying criteria met. |
| Interference | No significant interference up to specified concentrations. | Demonstrated no significant interference for all specified substances and parameters, up to the tested concentrations. (e.g., conjugated bilirubin up to 40 mg/dL, intralipid up to 500 mg/dL without suppression, etc.) |
| Metrological Traceability | Device traceable to internationally recognized reference methods via predicate. | Traceability established using predicate device (Sysmex XN) as reference, which is traceable to international reference methods for WBC, RBC, HGB, HCT, PLT. |
| Specimen Stability | Mean percentage difference within acceptable limits against baseline. | Results of all tested time points met the acceptance criteria, supporting an 8-hour blood sample stability. |
| Cartridge Lot-to-Lot Variability | Within-lot, between-lot, and total variability metrics within limits. | All within-lot, between-lot, and total %CV/StDev met the acceptance criteria. |
| QC Material – Lot-to-Lot Reproducibility | Pooled total CV/StDev for each QC parameter and level within limits. | The pooled total CV/StDev of the three lots met the acceptance criteria. |
| Method Comparison | Slope, intercept, and correlation coefficient from Deming fittings, and mean bias acceptable. | Results fully met the acceptance criteria for all reported parameters. |
| Flagging Comparison | Positive Percent Agreement, Negative Percent Agreement and Overall Agreement within acceptable range. | Positive Agreement: 91.9%, Negative Agreement: 95.3%, Overall Agreement: 93.7%; fully met acceptance criteria. |
| Reference Interval | Established/verified against literature values. | Reference intervals established for adults and verified for adolescents and children. |
2. Sample Sizes and Data Provenance
-
Test Set (Clinical Study Summary):
- Method Comparison: 481 venous whole blood samples.
- Flagging Comparison: 1,082 venous whole blood samples.
- Reference Interval: 253 adults, 46 adolescents, and 41 children.
- Data Provenance: The studies were conducted at CLIA-waived sites. The document does not specify the country of origin for the data but implies clinical settings within the US (where CLIA-waived labs would operate). The studies appear to be prospective to gather data specifically for device evaluation.
-
Training Set: The document does not explicitly mention a "training set" or "validation set" in the context of an AI/algorithm. The device is described as an "Automated Differential Cell Counter" utilizing fluorescent flow cytometry. This suggests a traditional IVD device, not necessarily one relying on an AI model trained on a large dataset in the way a deep learning algorithm would be. Therefore, information regarding training set size and ground truth establishment for a training set is not provided because it's likely not applicable to the device's development paradigm as described.
3. Number of Experts and Qualifications for Ground Truth
- Number of Experts: Not applicable or specified for ground truth establishment in the context of expert consensus reading on images. The device is an automated hematology analyzer. Ground truth is established by comparative methods and reference standards.
- Qualifications of Experts: The clinical studies were performed at "CLIA-waived testing sites" by "untrained operators" (for precision/reproducibility) and operators (for method comparison/flagging). The predicate device (Sysmex XN-series) served as the comparative method. The Metrological Traceability Study refers to established international reference methods and expert panels (e.g., ICSH Expert Panel on Cytometry, ICSH Expert Panel on Haemoglobinometry), which are the ultimate "experts" for the fundamental measurements.
4. Adjudication Method for the Test Set
The studies described are primarily analytical and clinical performance studies for an automated IVD device comparing it to a predicate device and reference methods, rather than reader studies for image-based diagnostic aids. Therefore, a multi-reader adjudication method (e.g., 2+1, 3+1) is not applicable or mentioned in this context. The "ground truth" is based on the performance of the predicate device/reference methods.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
No, a Multi-Reader Multi-Case (MRMC) comparative effectiveness study was not done. This type of study is typically performed for AI-assisted diagnostic imaging devices to assess how AI affects human reader performance. The Cito CBC System is an automated hematology analyzer, not an AI-based imaging diagnostic aid that assists human readers.
6. Standalone Algorithm Performance
This section is not directly applicable. The Cito CBC System is an integrated automated hematology analyzer, not a standalone algorithm. Its performance is measured as the output of the system (analyzer + cartridge). The performance studies evaluate the system's ability to accurately measure hematology parameters compared to reference methods. The "algorithm" (the instrument's internal measurement principles like flow cytometry and photometry) is intrinsically part of the device and its performance is demonstrated through the clinical and non-clinical studies.
7. Type of Ground Truth Used
The ground truth for evaluating the Cito CBC System's performance was established using:
- Comparative Method: The Sysmex XN Automated Hematology Analyzer (K112605), a legally marketed predicate device, was used as the comparative method in both the Method Comparison and Flagging Comparison studies.
- Reference Methods/Standards: For metrological traceability, the predicate device itself establishes traceability to internationally recognized reference methods (e.g., ICSH expert panel methods for WBC, RBC, HGB, HCT, PLT). These international standards serve as the ultimate ground truth for the measured parameters.
- Clinical Conditions/Abnormalities: For flagging comparison, samples covering a wide variety of abnormalities (distribution, morphological, other abnormal conditions) were used. The ground truth for these abnormalities would implicitly come from clinical diagnosis and the predicate device's flagging capabilities.
- Healthy Subjects: For the Reference Interval study, healthy subjects were enrolled, and reference intervals were established non-parametrically or verified against published literature.
8. Sample Size for the Training Set
As stated in point 2, the document does not describe the device as an AI/ML algorithm requiring a distinct "training set." The device is an automated instrument, and its development would typically involve engineering design, calibration, and validation rather than statistical "training" on a data set. Therefore, this information is not provided.
9. How the Ground Truth for the Training Set Was Established
As stated in points 2 and 8, the concept of a "training set" with established ground truth, as typically understood for AI/ML models, is not applicable to the description of the Cito CBC System provided
in the document.
§ 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.”