(91 days)
The BD FACSLyric™ flow cytometer is intended for use as an in vitro diagnostic device for immunophenotyping using up to six fluorescence detection channels and two light scatter channels using a blue (488-nm) and a red (640-nm) laser. It is intended for use with in vitro diagnostic (IVD) assays and software that are indicated for use with the instrument.
BD Multitest™ 6-color TBNK, BD Multitest™ IMK kit, BD Multitest™ CD3/CD8/CD45/CD4, and BD Multitest™ CD3/CD16+CD56/CD45/CD19, all with optional BD Trucount™ tubes, are intended for use on the BD FACSLyric flow cytometer with peripheral whole blood for immunophenotyping. These reagents are indicated for use in the immunological assessment of normal individuals, and patients having, or suspected of having, immune deficiency. These reagents determine the percentages and absolute counts of the following mature human lymphocyte subsets:
BD Multitest 6-color TBNK with optional BD Trucount tubes
- · T lymphocytes (CD3+)
- · B lymphocytes (CD19+)
- · Natural killer (NK) lymphocytes (CD3-CD16+ and/or CD56+)
- · Helper/inducer T lymphocytes (CD3+CD4+)
- · Suppressor/cytotoxic T lymphocytes (CD3+CD8+)
BD Multitest IMK kit with optional BD Trucount tubes
- · T lymphocytes (CD3+)
- · B lymphocytes (CD19+)
- · Natural killer (NK) lymphocytes (CD3-CD16+ and/or CD56+)
- · Helper/inducer T lymphocytes (CD3+CD4+)
- · Suppressor/cytotoxic T lymphocytes (CD3+CD8+)
BD Multitest CD3/CD8/CD45/CD4 with optional BD Trucount tubes
- · T lymphocytes (CD3+)
- · Suppressor/cytotoxic T lymphocytes (CD3+CD8+)
- · Helper/inducer T lymphocytes (CD3+CD4+)
BD Multitest CD3/CD16+CD56/CD45/CD19 with optional BD Trucount tubes
- · T lymphocytes (CD3+)
- · Natural killer (NK) lymphocytes (CD3-CD16+ and/or CD56+)
- · B lymphocytes (CD3-CD19+)
The BD FACSLyric Flow Cytometer consists of the following components.
- FACSLyric Flow Cytometer (3-1, 4-2, 4-2-2 and 4-3-3 optical configurations)
- FACSuite Clinical Software
- Multitest 6-Color Assay Modules
- Multitest 4-Color Assay Modules
- FC Beads 7-Color Kit
- CS&T Beads
- Multitest 6-Color TBNK
- Multitest IMK Kit
- . Multitest CD3/CD8/CD45/CD4
- Multitest CD3/CD16+CD56/CD45/CD19
- . Multi-Check Control
- . Multi-Check CD4 Low Control
- . Trucount Tubes
- Optional FACS Universal Loader
The system is an immunofluorescence assay system for identification and enumeration of lymphocyte subsets in peripheral whole blood. When blood is added to the monoclonal antibody reagent, the fluorochrome-labeled antibodies in the reagent bind specifically to lymphocvte surface antigens. During acquisition, the cells travel past one or more laser beams in a single file and scatter the laser light. The stained cells fluoresce. The scatter and fluorescence light is detected by the flow cytometer, separated by dichroic mirrors and optical filters, and then quantified with photomultiplier tubes (PMTs) to determine the percent lymphocyte of particular cell populations.
Multiple monoclonal antibodies each labeled with a different fluorochrome are contained within one reagent tube to simultaneously identify multiple lymphocyte subset populations. The use of Trucount tubes provides the absolute number of the fluorochrome-labeled antibody bound cells.
The provided text describes the BD FACSLyric™ Flow Cytometer, its indications for use, comparison to a predicate device (BD FACSCanto™ II system), and performance data supporting its substantial equivalency. Based on the provided document, here's an analysis of the acceptance criteria and study proving device performance:
Important Note: This document is an FDA 510(k) summary, which focuses on demonstrating substantial equivalence to a legally marketed predicate device rather than strictly presenting a clinical study design with explicit acceptance criteria for a novel AI/ML device. Therefore, some information (e.g., number of experts, adjudication methods, MRMC study effect size, sample size for training set, ground truth for training set) typically available for AI/ML device studies may not be directly available or applicable in this context. The study described focuses on demonstrating the performance of a new flow cytometer instrument rather than an AI/ML algorithm.
1. Table of Acceptance Criteria and Reported Device Performance
The document defines acceptance criteria primarily through "Objectives" for each study and "Results" indicating whether these objectives were met. The acceptance criteria are largely based on meeting performance requirements that demonstrate equivalency to the predicate device or established clinical laboratory guidelines (CLSI standards).
| Study Name | Objective (Acceptance Criteria) | Reported Device Performance (Results) |
|---|---|---|
| Bench Performance: | ||
| Intra-instrument Optical Configuration Equivalency | To demonstrate system level performance equivalency across the 3-1, 4-2, 4-2-2, and 4-3-3 optical configurations as measured by QC and setup performance parameters generated utilizing CS&T beads and FC beads. | System level optical equivalency was demonstrated between the four configurations. |
| Inter-instrument Optical Configuration Equivalency | To demonstrate performance equivalency between the 3-1, 4-2, 4-2-2, and 4-3-3 optical configurations of the FACSLyric through testing multiple instruments of different configurations (inter-instrument) using patient and normal donor samples stained with Multitest IMK kit and Multitest 6-Color TBNK in Trucount tubes. | The performance equivalency of the 6 IVD channels between the 3-1, 4-2, 4-2-2 and 4-3-3 optical configurations of the FACSLyric flow cytometer have been demonstrated. |
| Method Comparison | - To determine the method bias between the FACSLyric system and the FACSCanto II system on the determination of CD3+, etc., percentage and absolute counts (meeting acceptance criteria for bias). |
- To demonstrate equivalency between FACSLyric Universal Loader (UL) acquisition and FACSLyric manual acquisition. | The method bias between the FACSLyric and the FACSCanto II met the acceptance criteria. Equivalency between FACSLyric UL acquisition and Manual acquisition was demonstrated. |
| Within-site Precision | To evaluate the within-site precision performance of FACSLyric system using Multitest IMK kit and Multitest 6-Color TBNK with Trucount tubes (meeting within-run and total precision requirements). | All acceptance criteria were met. The within-site precision performance satisfied the within-run and total precision performance requirements. |
| Whole Blood Repeatability | To verify repeatability performance across all FACSLyric instruments of different configurations, using whole blood from patient and normal donor samples, stained with reagents (all lymphocyte subsets meeting %CV and SD acceptance criteria). | Repeatability performance was demonstrated across all instruments with different configurations. All lymphocyte subsets met %CV and SD acceptance criteria. |
| Linearity | To evaluate the linear range of the FACSLyric system using reagents (acceptable linear ranges established for each lymphocyte subset). | Acceptable linear ranges have been established for each lymphocyte subset for each of the Multitest reagents on FACSLyric system. |
| Sample Carryover | To determine percent sample carryover (less than or equal to 0.1% for low carryover and less than or equal to 0.5% for standard carryover). | All results met the acceptance criteria (less than or equal to 0.1% for low carryover and less than or equal to 0.5% for standard carryover) on all three FACSLyric instruments. Single SIT flush sufficient for low carryover. |
| Reagent Carryover | To verify minimal reagent carryover. | Results met the acceptance criteria. Amount of reagent carried over is well below the amount required for effective staining. |
| Detection Capability of LoB and LoD | To evaluate the limit of blank (LoB) and limit of detection (LoD) (LoB and LoD for CD4 lymphocyte subset absolute counts less than 50 cells/µL). | LoB and LoD for CD4 lymphocyte subset absolute counts were established and were less than 50 cells/µL. |
| Detection Capability of LoQ | To evaluate the limit of quantitation (LoQ) (LoQ for CD4 lymphocyte subset absolute counts less than 50 cells/µL). | The LoQ for the CD3+, CD3+CD4+, CD3+CD8+, CD19+, CD16+CD56+ and CD45+ lymphocyte subsets were established. Acceptance criteria were met and the LOQ is less than 50 cells/µL for CD4 lymphocyte subset absolute counts. |
| Setup and QC Performance | To verify that Setup & QC Performance meets pre-defined specifications. | All Setup & QC performance results met the acceptance criteria. |
| Setup and QC Stability | To verify the stability of system level Setup & QC. | All system level Setup & QC stability performance results met the pre-defined specifications. |
| Clinical Performance: | | |
| Method Comparison | To evaluate performance equivalence of the FACSLyric system and the FACSCanto II system on the determination of lymphocyte subsets. | The acceptance criteria for all lymphocyte subsets were met for the FACSLyric system. Differences were minimal and no bias trend observed when comparing manipulated vs non-manipulated specimens or different EDTA formulations. |
| Inter-laboratory Reproducibility | To evaluate inter-laboratory reproducibility for the FACSLyric system (variability for within run, between run, between day, between site, and total precision meeting 97.5% one-sided confidence interval compared to requirements). | Inter-laboratory reproducibility was carried out at four clinical sites. Variability met requirements and 97.5% one-sided confidence interval on precision was estimated and compared. |
| Reference Intervals | To re-establish the reference intervals of a normal male and female adult cohort (reference intervals established for all lymphocyte subsets). | Reference Intervals for all lymphocyte subsets were established. Differences observed between genders were not clinically significant. |
| Specimen Stability | To generate data to support stability of venous whole blood with EDTA anticoagulant when testing reagents on the FACSLyric system (supporting stability claims for Age of Blood and Age of Stain). | The results support the claim of up to 24 hours Age of Blood and 6 hours Age of Stain for Multitest 6-Color TBNK, and up to 48 hours Age of Blood and 24 hours Age of Stain for Multitest IMK kit (including other Multitest assays) on FACSLyric system. |
2. Sample Sizes Used for the Test Set and Data Provenance
- Inter-instrument Optical Configuration Equivalency & Whole Blood Repeatability: Used patient and normal donor samples from unspecified locations.
- Method Comparison (Bench Study): Samples sourced from unspecified locations.
- Method Comparison (Clinical Study): A total of 332 specimens were enrolled for Multitest 6-Color TBNK (297 evaluable), and 368 specimens were enrolled for Multitest IMK kit (336 evaluable) at 5 clinical sites. These were remnant, de-linked patient specimens. The provenance is not explicitly stated as retrospective or prospective, but "remnant, de-linked patient specimens" typically implies a retrospective use of existing samples.
- Inter-laboratory Reproducibility: Used a single lot of Streck CD-Chex Plus process control material at four clinical sites. (Not a human patient sample size).
- Reference Intervals: A total of 136 subjects were enrolled (134 evaluable for Multitest 6-Color TBNK and 130 evaluable for Multitest IMK kit) from one clinical site. These were prospectively procured and de-linked donor specimens.
- Specimen Stability: A total of 227 specimens were enrolled for each of the reagents from two clinical sites. These were prospectively procured and de-linked patient specimens.
Data Provenance (General): While specific countries are not mentioned, the document is an FDA submission for the US market, implying that the studies were conducted in accordance with US regulatory requirements, likely involving US-based clinical sites. The data included both normal donor and patient samples, and were both prospectively and retrospectively collected (e.g., remnant, de-linked specimens).
3. Number of Experts Used to Establish Ground Truth and Qualifications:
This document describes a flow cytometer and associated reagents, not an AI/ML algorithm that requires expert labeling of images or complex data for ground truth. The "ground truth" for this type of device is the accurate measurement and enumeration of cell subsets, which is compared against results from a predicate device or validated laboratory methods. Therefore, the concept of "experts establishing ground truth for the test set" as typically understood in AI/ML validation studies (e.g., radiologists annotating images) is not directly applicable here. The accuracy of the cell counts would be intrinsically tied to the performance of the predicate device (BD FACSCanto II system) and the established clinical laboratory guidelines (CLSI standards) used for comparison.
4. Adjudication Method for the Test Set:
Not applicable in the context of this device and study type. The studies involve quantitative measurements and comparisons against established parameters or a predicate device, rather than subjective interpretations requiring adjudication among multiple readers.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study:
No, an MRMC comparative effectiveness study, as typically done for AI/ML devices assisting human readers in diagnostic tasks, was not conducted or described. This submission relates to a flow cytometer instrument, where performance is measured by its ability to accurately count and phenotype cells, rather than its effect on human interpretations of complex data like medical images.
6. Standalone (Algorithm Only) Performance:
Not applicable. The device is a "Flow Cytometer," an automated instrument for in vitro diagnostic use. Its performance is inherently "standalone" in executing its function of cell counting and phenotyping. There is no separate "algorithm-only" component as might be found in an AI/ML software. The software (FACSuite Clinical Software) manages the instrument and data analysis for the user, and its performance is evaluated as part of the overall system.
7. Type of Ground Truth Used:
The ground truth is established by:
- Predicate Device Comparison: The performance of the BD FACSLyric™ system is compared to a legally marketed predicate device, the BD FACSCanto™ II system. This is a primary form of "ground truth" for demonstrating substantial equivalence.
- Established Clinical Laboratory Standards: Adherence to various Clinical and Laboratory Standards Institute (CLSI) guidelines (e.g., CLSI EP09-A3 for Method Comparison and Bias Estimation, CLSI EP05-A3 for Precision, CLSI EP6-A for Linearity, CLSI H26-A2 for Carryover, CLSI EP17-A2 for Detection Capability, CLSI EP28-A3c for Reference Intervals) serves as the "ground truth" for acceptable analytical performance. These standards provide accepted methodologies and performance metrics for laboratory assays.
- Quantitative Measurement: The device measures percentages and absolute counts of lymphocyte subsets. The "ground truth" for these measurements is the true biological count in the sample, which is assessed through rigorous validation encompassing precision, linearity, limits of detection, and comparison to a well-characterized predicate.
8. Sample Size for the Training Set:
Not applicable. This is not an AI/ML device, and there is no mention of a "training set" for an algorithm. The development and validation of flow cytometers rely on engineering principles, analytical studies, and clinical performance studies, not on training data for a machine learning model.
9. How the Ground Truth for the Training Set Was Established:
Not applicable, as there is no training set for an AI/ML algorithm.
§ 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.”