(113 days)
BD Multitest 6-Color TBNK reagent with BD Trucount tubes is intended for in vitro diagnostic use with the BD FACSCanto system to identify and determine the percentages and absolute counts of T, B, and natural killer (NK) cells as well as the CD4 and CD8 subpopulations of T cells in peripheral blood.
The BD Multitest 6-Color TBNK reagent is a six-color direct immunofluorescence reagent for use with the BD FACSCanto system to identify and determine the percentages and absolute counts (using BD Trucount tubes) of T, B, and natural killer (NK) cells as well as the CD4 and CD8 subpopulations of T cells in peripheral blood.
When a known volume of whole blood is added to the reagent in a BD Trucount tube, the fluorochrome-labeled antibodies in the reagent bind specifically to leucocyte surface antigens. The stained samples are treated with BD FACS lysing solution to lyse erythrocytes, and the lyophilized pellet in the BD Trucount tube dissolves, releasing a known number of fluorescent beads.
During acquisition, the cells and beads travel past two laser beams and scatter the laser light. The stained cells and beads fluoresce at different intensities. These scatter and fluorescence signals, detected by the flow cytometer, provide information about each cell's size, internal complexity, and relative fluorescence intensity. During analysis, the absolute number (cells/uL) of positive cells in the sample can be determined by comparing cellular events to bead events.
Here's an analysis of the provided text, focusing on the acceptance criteria and the study that proves the device meets them:
1. Table of Acceptance Criteria and Reported Device Performance
The acceptance criteria for this device appear to be primarily focused on its accuracy, precision, linearity, and stability in comparison to a predicate device. The performance data is presented in terms of mean bias for accuracy and standard deviation/coefficient of variation for precision.
| Metric (Acceptance Criteria) | Lymphocyte Subset | Reported Device Performance (Mean Bias % or Standard Deviation (SD) / %CV) |
|---|---|---|
| Accuracy (Mean Bias %) | ||
| (Compared to Predicate Device) | CD4 (Percentage) | 0.1 (-0.1, 0.2) |
| CD8 (Percentage) | -0.8 (-1.0, -0.5) | |
| CD3 (Percentage) | -0.2 (-0.4, 0.0) | |
| CD19 (Percentage) | 0.3 (0.2, 0.4) | |
| CD16+CD56 (Percentage) | -0.1 (-0.3, 0.0) | |
| CD4 (Absolute Count) | -2.7 (-4.2, -1.3) | |
| CD8 (Absolute Count) | -3.5 (-4.4, -2.6) | |
| CD3 (Absolute Count) | -1.9 (-2.6, -1.2) | |
| CD19 (Absolute Count) | 1.8 (0.3, 3.3) | |
| CD16+CD56 (Absolute Count) | -2.3 (-4.1, 0.5) | |
| Precision (Repeatability - SD) | ||
| (Within-Device Precision for Percentages) | CD4 (Low Sample) | 0.64 |
| CD4 (Normal Sample) | 0.95 | |
| CD8 (Low Sample) | 1.07 | |
| CD8 (Normal Sample) | 0.65 | |
| CD3 (Low Sample) | 1.17 | |
| CD3 (Normal Sample) | 0.86 | |
| CD19 (Low Sample) | 0.89 | |
| CD19 (Normal Sample) | 0.62 | |
| CD16+CD56 (Low Sample) | 0.90 | |
| CD16+CD56 (Normal Sample) | 0.61 | |
| Precision (Repeatability - %CV) | ||
| (Within-Device Precision for Absolute Counts) | CD4 (Low Sample) | 7.6 |
| CD4 (Normal Sample) | 4.7 | |
| CD8 (Low Sample) | 4.1 | |
| CD8 (Normal Sample) | 4.7 | |
| CD3 (Low Sample) | 4.0 | |
| CD3 (Normal Sample) | 4.2 | |
| CD19 (Low Sample) | 5.7 | |
| CD19 (Normal Sample) | 5.3 | |
| CD16+CD56 (Low Sample) | 7.0 | |
| CD16+CD56 (Normal Sample) | 7.9 | |
| Linearity (R2) | CD4 | 0.998 |
| CD8 | 0.991 | |
| CD3 | 0.996 | |
| CD19 | 0.989 | |
| CD16+CD56 | 0.999 | |
| Sample Stability | Anticoagulated blood | Stained within 24 hours of draw and analyzed within 6 hours of staining |
| Stain Stability | Stained samples | Analyzed within 6 hours of staining (implied from above) |
Note: The document states "Substantial equivalence and the performance of BD Multitest 6-color TBNK reagent with BD Trucount tubes have been demonstrated through accuracy, precision, linearity, and sample and stain stability studies." The acceptance criteria are implicitly met if the reported performance data falls within acceptable ranges relative to the predicate, as interpreted by the FDA's substantial equivalence determination.
2. Sample Size Used for the Test Set and Data Provenance
- Sample Size for Accuracy Study (Test Set):
n = 117for all lymphocyte subsets (CD4, CD8, CD3, CD19, CD16+CD56) for both percentages and absolute counts. - Sample Size for Precision Study (Test Set):
n = 42for all lymphocyte subsets for both percentages and absolute counts across "Low Sample" and "Normal Sample" groups. - Data Provenance: The document does not explicitly state the country of origin or whether the data was retrospective or prospective. Given the nature of medical device submissions in the US, it is highly probable that the studies were conducted in the US, and typically prospective data is preferred for performance validation. However, this is not explicitly mentioned.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
This type of device (automated differential cell counter) does not rely on expert interpretation of images or other subjective data for ground truth. The "ground truth" for the accuracy study is established by comparison to a legally marketed predicate device (BD Multitest IMK kit with BD FACSCanto system and clinical software). The predicate device itself has established performance characteristics, and the ground truth for that device would have been established through methods like flow cytometry standards, reference methods, or clinical correlation. No human experts are used to establish ground truth in the way a radiologist might for an imaging AI.
4. Adjudication Method (for the test set)
Not applicable. As explained in point 3, the ground truth is established by the predicate device's measurements, not by human interpretation or adjudication.
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
Not applicable. This device is an automated diagnostic assay (a reagent/instrument system) for quantifying cell populations, not an AI-assisted diagnostic imaging tool or a system that requires human interpretation in the same way. Therefore, an MRMC study comparing human readers with AI assistance is not relevant to its evaluation.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) was done
Yes, the studies presented (accuracy, precision, linearity) represent the standalone performance of the device system (reagent + instrument + software). The results are generated directly by the system without human interpretation influencing the quantification of the lymphocyte subsets. The comparison is made against another device system (the predicate).
7. The Type of Ground Truth Used
The ground truth for the accuracy study was the measurements obtained from the predicate device, the BD Multitest IMK kit used with the BD FACSCanto system and BD FACSCanto clinical software (K041074). This is referred to as "method comparison."
8. The Sample Size for the Training Set
The document does not explicitly mention a "training set" in the context of machine learning. This device is a flow cytometry assay system, not an AI/ML algorithm that is typically "trained" on data. Its performance is based on the biochemical reactions of antibodies and the physical principles of flow cytometry. If there were any internal device calibration or optimization data, it is not described here as a "training set."
9. How the Ground Truth for the Training Set Was Established
Not applicable, as there is no explicitly defined "training set" in the context of an AI/ML algorithm for this device. The system functions based on established biological and chemical principles, not on a machine learning model that requires a trained ground truth dataset in the conventional sense. The "ground truth" for the development of such assays would derive from established laboratory standards and reference methods for cell enumeration and phenotyping.
§ 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.”