(30 days)
The COULTER® LH 750 Hematology Analyzer is a quantitative, automated hematology Analyzer and leukocyte differential counter For In Vitro Diagnostic Use in clinical laboratories. The COULTER® LH 750 Hematology Analyzer also provides automated Reticulocyte analysis and enumeration of nucleated red blood cells (NRBCs) in whole blood and white blood cells (WBCs) and red blood cells (RBCs) in body fluids.
The LH 700 Series Body Fluid Application is a procedure for obtaining in vitro quantitative determinations of leukocytes (WBC) and erythrocytes (RBC) in cerebrospinal fluid, serous fluids, and synovial fluid, using a COULTER LH 700 Series Hematology Analyzer.
The product is an automated hematology analyzer capable of supplying a complete blood cell analysis and includes a differential leukocyte cell count. The product also provides automated reticulocyte analysis, enumeration of nucleated red blood cells (NRBCs) in whole blood and leukocytes (WBC) and erythrocytes (RBC) in cerebrospinal fluid, serous fluids, and synovial fluid.
Here's an analysis of the provided text regarding the acceptance criteria and supporting study for the COULTER® LH 750 Hematology Analyzer's body fluids application:
1. Table of Acceptance Criteria and Reported Device Performance
The provided document describes a modification to the existing COULTER® LH 750 Hematology Analyzer, specifically related to the stability of synovial and serous fluid samples. It doesn't detail the full acceptance criteria for the original device's general performance (e.g., accuracy, precision for all blood cell analysis), but rather focuses on the extended sample stability for specific fluid types.
Therefore, the table below reflects the specific acceptance criteria and reported performance relevant to this modification.
| Acceptance Criterion (for modification) | Reported Device Performance (validated performance) |
|---|---|
| Synovial fluid sample stability | 8 hours (previously 1 hour) |
| Serous fluid sample stability | 8 hours (previously 24 hours - note a decrease, not an increase in stability approval for serous fluids) |
Note: The document states: "...to indicate a sample stability of eight (8) hours for synovial fluid analysis (rather than 1 hour) and eight (8) hours for serous fluid analysis (rather than 24 hours) to reflect actual validated performance." This implies that for serous fluid, while the proposed labeling change was from 24 hours to 8 hours, the new validated performance is 8 hours. This isn't an improvement in stability for serous fluids compared to the prior claim, but rather a correction to reflect actual validated performance, which now matches synovial fluid.
2. Sample Size Used for the Test Set and Data Provenance
The document does not explicitly state the sample size used for the validation study that established the new sample stability times.
It also does not directly specify the provenance (country of origin, retrospective/prospective) of the data. However, as it's an FDA submission for a device marketed in the US, it's highly probable the data was generated within the US or under US regulatory guidelines. Given the context of "actual validated performance," it implies a prospective validation study was conducted to determine these new stability parameters.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of those Experts
The document does not mention the use of experts to establish ground truth in the context of this sample stability study. This type of validation typically involves laboratory experiments comparing measurements taken at different time points, rather than subjective expert interpretation of results. The "ground truth" would be objective measurements from fresh samples. If clinicians were involved, it would likely be for reviewing the clinical implications, not for establishing the instrument's analytical performance on stability.
4. Adjudication Method for the Test Set
The document does not describe an adjudication method. Adjudication is usually relevant when multiple experts provide subjective assessments that need to be reconciled. In a study validating sample stability of a hematology analyzer, the "ground truth" (i.e., whether a sample's parameters changed significantly over time) is determined by quantitative measurements and statistical analysis, not by expert consensus 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
No MRMC comparative effectiveness study was done, nor is it applicable here. This submission is for a modification to an automated hematology analyzer, not an AI-powered diagnostic imaging tool or a system involving human interpretation with AI assistance. The device fully automates the analysis.
6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done
The entire operation of the COULTER® LH 750 Hematology Analyzer for cell counting and differentiation is standalone (algorithm only without human-in-the-loop performance). The device is the algorithm and analytical system; human interaction is for sample loading, maintenance, and result interpretation, but not for the primary measurement process itself. The modification discussed here (sample stability) directly pertains to the standalone performance of the analyzer with respect to sample integrity over time.
7. The Type of Ground Truth Used (expert consensus, pathology, outcomes data, etc.)
For the sample stability study, the ground truth would be established through quantitative laboratory measurements on fresh samples and samples stored for different durations. The "ground truth" for a stable sample is that its measured parameters (e.g., WBC, RBC counts) do not significantly deviate from the initial measurement taken at time zero, within pre-defined analytical variation limits. This is an objective, measurement-based ground truth, not dependent on expert consensus or pathology in the conventional sense.
8. The Sample Size for the Training Set
The document does not mention a "training set" in the context of this sample stability modification. Hematology analyzers, especially those based on electrical impedance (Coulter Principle) and VCS technology, are generally rule-based or empirically developed, not typically "trained" using machine learning in the way an AI algorithm for image recognition would be. The validation described is about confirming the analytical stability of samples over time when processed by the existing device software and hardware.
9. How the Ground Truth for the Training Set Was Established
As there is no mention of a training set for this specific modification and device type, this question is not applicable. The device's core functionality and its initial ground truth for cell identification and counting would have been established through extensive analytical validation against reference methods (e.g., manual microscopy, other established technologies) during its original development. This particular submission concerns a change in labeling claim based on new validation data regarding sample stability.
§ 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.”