(116 days)
BD Multitest™ 6-color TBNK reagent with optional BD Trucount™ tubes is a sixcolor direct immunofluorescence reagent for use with BD FACSCanto™ and BD FACSCanto™ II flow cytometers 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.
BD Multitest 6-color TBNK reagent and BD Trucount tubes can be used with the BD FACS™ Loader.
Human lymphocytes can be divided into three major subset populations based on their biologic function and cell-surface antigen expression: T Ivmphocytes (CD3+), B lymphocytes (CD19+), and Natural Killer (NK) cells (CD16+ and/or CD56+). CD3+ T lymphocytes can be further divided into CD4+ T lymphocytes and CD8+ T lymphocytes.
BD Multitest 6-Color TBNK Reagent is a monoclonal antibody cocktail of CD3-FITC/ CD16-PE + CD56-PE/ CD45-PerCP-Cy5.5/ CD4-PE-Cy7/ CD19-APC/ CD8-APC-Cy7.
When the reagent is used to stain a known volume of whole blood, 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 prior to acquisition and analysis on the BD FACSCanto or BD FACSCanto II flow cytometer. During acquisition, the cells travel past two spatially separated laser beams. The cells scatter the laser light and the cell-bound fluorochrome-labeled antibodies fluoresce. These scatter and fluorescence signals are detected by the flow cytometer and provide information about the cell's relative size, internal complexity and fluorescence intensity. During analysis by BD FACSCanto clinical software, the lymphocyte population percentages are determined. Lymphocyte population absolute counts may be determined if Ivmphocvte data from another method is manually entered.
Here's an analysis of the provided text regarding the acceptance criteria and the study proving the device meets them:
1. Table of Acceptance Criteria and Reported Device Performance
| Performance Characteristic | Acceptance Criteria | Reported Device Performance |
|---|---|---|
| Clinical Precision | The upper one-sided 95% confidence bound on the standard deviation (SD) for the within-device precision must be ≤2.5 on the investigational system for lymphocyte population percentages. | "Lymphocyte population percentages met the predetermined acceptance criteria: the upper one-sided 95% confidence bound on the standard deviation (SD) for the within-device precision must be ≤2.5 on the investigational system." (Excerpt implies it met the criteria, as it states it "met" them and then reiterates the criteria). |
| Clinical Method Comparison | The 95% confidence interval (CI) of the mean difference between the investigational and predicate systems must be within an absolute ±3% or a relative ±10% of the predicate mean, whichever is greater, for lymphocyte population percentages. | "Lymphocyte population percentages, in comparison to the predicate, met the predetermined acceptance criteria: the 95% confidence interval (CI) of the mean difference between the investigational and predicate systems must be within an absolute ±3% or a relative ±10% of the predicate mean, whichever is greater." (Excerpt implies it met the criteria). |
| Non-Clinical Method Comparison | The 95% CI of the mean difference between the test and predicate population shall be within +/-3% absolute or +/-10% relative to the predicate mean, whichever is greater, for lymphocyte population percentages. | "Lymphocyte population percentages, in comparison to the predicate, met the predetermined acceptance criteria: the 95% Cl of the mean difference between the test and predicate population shall be within +/-3% absolute or +/-10% relative to the predicate mean, whichever is greater." (Excerpt implies it met the criteria). |
| Non-Clinical Software Functionality | Predetermined functional requirements for software development (including functionality such as cytometer setup & optimization, acquisition/analysis worklist, Lab Manager, user preferences, running a QC sample, and user interface) for BD FACSCanto clinical software version 2.4. | "BD FACSCanto clinical software version 2.4 met the predetermined functional requirements for software development..." (Excerpt implies it met the criteria). |
| Non-Clinical File-Based Equivalency for Software | Predetermined functional requirements for providing results equivalent to the results from the previously released version of the software (BD FACSCanto clinical software version 2.2) for BD FACSCanto clinical software version 2.4. | "BD FACSCanto clinical software version 2.4 met the predetermined functional requirements for providing results equivalent to the results from the previously released version of the software, (BD FACSCanto clinical software version 2.2)." (Excerpt implies it met the criteria). |
2. Sample Size Used for the Test Set and Data Provenance
The document does not specify the sample size used for the clinical test sets in either the precision or method comparison studies. It also does not explicitly state the country of origin or whether the data was retrospective or prospective. It generally refers to these as "clinical studies."
For non-clinical studies (software functionality and file-based equivalency), it's implied that various tests were performed, but no sample sizes or data provenance are provided.
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 device in question is a reagent and flow cytometer system for identifying cell populations, and the "ground truth" seems to be established through comparison to a predicate device and internal performance metrics, rather than expert interpretation of images or other data.
4. Adjudication Method for the Test Set
This information is not applicable or provided. The studies described involve quantitative measurements and comparisons to a predicate device and predefined statistical criteria, not subjective human adjudication of results in the way it would be used in image-based diagnostic studies.
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
There is no mention of a Multi Reader Multi Case (MRMC) comparative effectiveness study, nor is there any discussion of human readers or AI assistance. This device is an automated diagnostic assay, not an AI-powered image analysis tool for human readers.
6. If a Standalone (i.e. algorithm only without human-in-the-loop performance) was done
Yes, the performance studies described are essentially standalone in terms of the device's function. The "investigational system" (BD Multitest 6-color TBNK Reagent with BD FACSCanto/II flow cytometers) is evaluated directly for its precision and agreement with a predicate device. While a human operates the equipment, the "performance" refers to the automated output of lymphocyte percentages and counts by the system itself.
7. The Type of Ground Truth Used (expert consensus, pathology, outcomes data, etc.)
The primary "ground truth" implicitly used for the clinical and non-clinical method comparison studies is the predicate device (BD Multitest™ 6-Color TBNK with Trucount™ Tubes [510(k) # K060375]). The new device's performance is compared against this legally marketed and accepted predicate to establish substantial equivalence. For precision, the ground truth is statistical variability within the system itself. For software, the ground truth is its ability to meet specified functional requirements and provide equivalent results to a previous software version.
8. The Sample Size for the Training Set
The document does not mention a "training set" in the context of machine learning or AI. As this is a reagent and flow cytometry system, it operates based on established immunological principles and chemical reactions, not on algorithms that are "trained" on data in the modern AI sense.
9. How the Ground Truth for the Training Set Was Established
As there is no mention of a "training set" in the context of an AI/machine learning model, this question is not applicable. The device's operation is based on pre-defined scientific principles and reagent characteristics.
§ 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.”