(62 days)
The COULTER® A•T™ 5diff Cap Pierce (CP) hematology analyzer is a 26-parameter, fully automated hematology analyzer including a five-part leukocyte differential counter capable of analyzing samples in a closed vial or open vial mode.
The COULTER® A • T™ 5diff Cap Pierce (CP) is a moderate cost 5-part differential hematology analyzer that consists of the analyzer, a personal computer (PC) workstation and a printer.
Acceptance Criteria and Device Performance Study for COULTER® A•T™ 5diff Cap Pierce (CP)
This document describes the acceptance criteria and a detailed study supporting the performance of the COULTER® A•T™ 5diff Cap Pierce (CP) hematology analyzer.
1. Acceptance Criteria and Reported Device Performance
The provided document does not explicitly present a table of predetermined acceptance criteria with corresponding performance results in a consolidated format. However, based on the context of a 510(k) submission for an automated differential cell counter, the primary acceptance involves demonstrating substantial equivalence to predicate devices. This implies meeting or performing comparably to the established performance of the legally marketed predicate devices, specifically the COULTER® HmX with Autoloader (K922704/A1) and the COULTER® A•T™ 5diff Autoloader (AL) (K030291, K032013).
The summary of the performance data states: "The data in the Premarket Notification on safety and effectiveness supports a finding of substantial equivalence studies of the COULTER® A^T™ 5diff Cap Pierce (CP) Hematology Analyzer to products already in commercial distribution."
While specific numerical acceptance criteria (e.g., precision, accuracy, linearity targets) and detailed performance metrics are not provided in this summary, the FDA's clearance (K042173) confirms that the submitted data met the regulatory requirements for demonstrating substantial equivalence. The comparison table of features (parameters measured, principles of measurement, sample volume, throughput) between the candidate device and the predicates indicates that the COULTER® A•T™ 5diff Cap Pierce (CP) offers largely the same core functionality and technology as its predicates. The key new feature for the COULTER® A•T™ 5diff CP is the "Cap Pierce" capability, allowing closed-vial sampling, which would have been a primary area for demonstrating equivalent performance to ensure it doesn't negatively impact the analytical results.
Inferences on Acceptance Criteria (Typical for such devices):
Based on typical FDA requirements for automated differential cell counters, acceptance criteria would generally revolve around:
- Accuracy/Correlation: High correlation coefficients (e.g., r > 0.95 or 0.98) and minimal bias when comparing results obtained from the new device against the predicate devices or reference methods (e.g., manual differential counts adjudicated by experts) for all reported parameters (WBC, RBC, Hgb, Hct, MCV, MCH, MCHC, RDW, Plt, MPV, Pct, Lymphocyte %, Monocyte %, Neutrophil %, Eosinophil %, Basophil %).
- Precision (Reproducibility & Repeatability): Low coefficients of variation (CV%) for all measured parameters, indicating consistent results over multiple measurements.
- Linearity/Reportable Range: Demonstrating accurate measurements across the clinically relevant analytical range for each parameter.
- Carryover: Minimal transfer of sample material from one run to the next.
- Interference Studies: Performance unaffected by common interfering substances.
- Reference Intervals: Establishing appropriate normal ranges.
- Warning/Flagging Performance: Correct identification and flagging of abnormal or immature cells.
Reported Device Performance:
The document explicitly states that the "data in the Premarket Notification on safety and effectiveness supports a finding of substantial equivalence." This means the device's performance, as detailed in the full submission, met the necessary thresholds to demonstrate it is as safe and effective as the predicate devices. Without access to the full Premarket Notification, specific numerical performance results cannot be reported here.
2. Sample Size and Data Provenance for the Test Set
The provided summary does not specify the sample size used for the test set in the substantial equivalence studies. It also does not explicitly mention the data provenance (e.g., country of origin, retrospective or prospective).
For a 510(k) submission, clinical validity and analytical validity studies are typically conducted. These studies would involve analyzing a sufficient number of patient samples (e.g., hundreds to thousands, including normal and abnormal samples) to demonstrate statistical equivalence. The samples are generally collected prospectively in a clinical laboratory setting to reflect real-world conditions.
3. Number and Qualifications of Experts for Ground Truth
The summary does not specify the number of experts or their qualifications used to establish ground truth for the test set.
For automated differential cell counters, ground truth for leukocyte differential counts and abnormal cell flagging is typically established by:
- Manual microscopy examination: Performed by highly experienced, board-certified clinical laboratory scientists (medical technologists/technicians) specializing in hematology.
- Pathologist review: In cases of disagreement or complex morphology, a board-certified hematopathologist (e.g., with 10+ years of experience) would adjudicate.
4. Adjudication Method for the Test Set
The document does not specify the adjudication method used for the test set.
Common adjudication methods for establishing ground truth in hematology include:
- Consensus of 2 out of 3 experts: If three experts independently classify a cell or smear, the majority opinion forms the ground truth.
- One senior expert review: A single highly experienced expert's opinion may serve as ground truth.
- Two-plus-one (2+1): Two initial readers, and if they disagree, a third senior reader resolves the discrepancy.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
The provided text does not indicate that a Multi-Reader Multi-Case (MRMC) comparative effectiveness study was performed to assess the improvement of human readers with vs. without AI assistance. The COULTER® A•T™ 5diff Cap Pierce (CP) is an automated analyzer, not a system primarily designed to provide AI assistance to human readers for interpretation, but rather to perform the differential count itself. Its purpose is to screen samples, flagging those that may require further manual review. Therefore, this type of MRMC study would be less relevant for this device.
6. Standalone (Algorithm Only) Performance Study
Yes, a standalone performance study was clearly performed. The entire premise of the 510(k) submission for the COULTER® A•T™ 5diff Cap Pierce (CP) is to demonstrate the performance of the algorithm and instrument as a standalone system. The device is an "Automated Differential Cell Counter," meaning its primary function is to perform the blood cell counts and differentials without human intervention for each count, then present the results. The "Summary of Performance Data" refers to studies of the device itself.
7. Type of Ground Truth Used
The type of ground truth used would typically be a combination of:
- Reference instrument comparison: Comparing results against a legally marketed predicate device (e.g., COULTER® HmX or A•T™ 5diff AL) known for its established performance. This is the primary method for demonstrating "substantial equivalence."
- Expert Consensus (Manual Microscopy): For parameters like leukocyte differential and abnormal cell identification, manual microscopy performed by qualified laboratory personnel, often adjudicated by expert consensus, would be used as the gold standard.
- Reference Methods: For certain parameters (e.g., hemoglobin), calibrated reference methods might be used.
The document implicitly relies on the established performance of its predicate devices, indicating that the ground truth for validating its substantial equivalence would likely involve a direct comparison to these predicate instruments and standard laboratory reference methods.
8. Sample Size for the Training Set
The provided summary does not specify the sample size for the training set. If this device utilized a machine learning algorithm for its differential classification (which is common for modern differential counters), a large number of diverse samples would be required for training the algorithm.
9. How the Ground Truth for the Training Set Was Established
The document does not specify how the ground truth for the training set was established.
For a hematology analyzer employing a differential algorithm, the ground truth for training data would typically be established similarly to the test set:
- Manual Microscopy with Expert Review: Each cell in the training samples would be identified and classified by highly experienced medical technologists or hematopathologists using manual microscopy, often with a consensus process (e.g., 2 out of 3 experts agreeing) to ensure accuracy.
- Correlation with Reference Methods: For quantitative parameters, the results would be correlated with established reference methods.
- Large, Diverse Dataset: The training set would need to include a wide range of normal and abnormal blood samples, covering various pathologies, cell types, and demographic variations, to ensure the algorithm learns to accurately classify different cellular morphologies.
§ 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.”