ABBOTT CELL-DYN 4000 SYSTEM by ABBOTT DIAGNOSTICS

The CELL-DYN® 4000 System is a fully automated hematology analyzer intended for in-vitro diagnostic use in the clinical hematology laboratory of a hospital, medical clinic, or reference laboratory.

Device Description

The CELL-DYN® 4000 System has five main modules: the Analyzer, which aspirates, dilutes and analyzes each whole blood specimen; the Autoloader, which automatically identifies, mixes, and presents specimens for processing; the Pneumatic Unit, which controls fluid movement in the Analyzer and tube movement in the Autoloader; the Data Station, which controls all system processing and provides the primary operator interface with the system; and the Color Printer, which generates reports automatically or on demand.

AI/ML Overview

The provided text describes the CELL-DYN® 4000 System and its substantial equivalence to other existing hematology analyzers. However, it does not contain a specific study proving the device meets acceptance criteria in the format typically expected. Instead, it makes claims about "accuracy, precision, and linearity" demonstrating performance to "manufacturer's specifications" and supports substantial equivalence to predicate devices.

Therefore, many of the requested fields cannot be directly extracted from the provided text. I will fill in what can be inferred or explicitly stated.

Acceptance Criteria and Reported Device Performance

The document states that the "accuracy, precision, and linearity data shows performance to manufacturer's specifications." However, the specific manufacturer's specifications (acceptance criteria) for these parameters are not explicitly provided in the text. The text primarily focuses on demonstrating substantial equivalence to predicate devices rather than listing detailed performance metrics against predefined acceptance thresholds.

What is explicit is the claim of substantial equivalence to:

Abbott CELL-DYN 3500 System for hemogram and white cell (WBC) differential parameters.
Becton Dickinson FACScan™ Flow Cytometer ReticCOUNT™ Reticulocyte Enumeration Software for reticulocytes.
Manual microscopic WBC differential count for enumeration of nucleated red blood cells (NRBCs).

Without the specific manufacturer's specifications, a table of acceptance criteria and reported performance cannot be fully constructed.

Parameter Category	Acceptance Criteria (Manufacturer's Specifications)	Reported Device Performance (Claim)
Hemogram	Not explicitly stated	Meets manufacturer's specifications for accuracy, precision, and linearity; Substantially equivalent to Abbott CELL-DYN 3500.
WBC Differential	Not explicitly stated	Meets manufacturer's specifications for accuracy, precision, and linearity; Substantially equivalent to Abbott CELL-DYN 3500.
Reticulocytes	Not explicitly stated	Meets manufacturer's specifications for accuracy, precision, and linearity; Substantially equivalent to Becton Dickinson FACScan.
NRBCs	Not explicitly stated	Substantially equivalent to manual microscopic WBC differential count.
Accuracy	Not explicitly stated	Performance to manufacturer's specifications.
Precision	Not explicitly stated	Performance to manufacturer's specifications.
Linearity	Not explicitly stated	Performance to manufacturer's specifications.
Carryover	Not explicitly stated	Performance to manufacturer's specifications.

Study Details

Sample size used for the test set and the data provenance (e.g. country of origin of the data, retrospective or prospective):
- The document mentions "The data complied to support the claim... includes accuracy, precision, linearity, and carryover." However, specific sample sizes for these tests are not provided.
- The data provenance (country of origin, retrospective/prospective) is not specified in the provided text.
Number of experts used to establish the ground truth for the test set and the qualifications of those experts:
- For NRBC enumeration, equivalence is demonstrated by comparison to the "manual microscopic WBC differential count." This usually implies human expert review, but the number of experts and their qualifications are not specified.
- For other parameters, the ground truth seems to be established by comparison to predicate devices, not typically by human experts as a primary ground truth.
Adjudication method (e.g. 2+1, 3+1, none) for the test set:
- Not specified.
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 study was mentioned. This device is an automated hematology analyzer, not an AI-assisted diagnostic tool for human readers.
If a standalone (i.e. algorithm only without human-in-the-loop performance) was done:
- Yes, the entire submission describes the standalone performance of the CELL-DYN® 4000 System, which is a fully automated hematology analyzer. Its performance is measured against predicate devices and manufacturer's specifications.
The type of ground truth used (expert consensus, pathology, outcomes data, etc):
- The ground truth for demonstrating substantial equivalence is primarily based on:
  - Measurements from predicate devices: Abbott CELL-DYN 3500 System and Becton Dickinson FACScan.
  - Manual microscopic WBC differential count for NRBCs.
  - Manufacturer's internal specifications for accuracy, precision, and linearity.
The sample size for the training set:
- This being a 510(k) submission for a medical device (analyzer), rather than a machine learning algorithm, the concept of a "training set" in the context of AI is not (and would not be) explicitly discussed. The device's operation is based on established principles of flow cytometry rather than a trained AI model. No training set information is provided.
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/ML algorithm, this question is not applicable based on the provided text.

Summary

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CELL-DYN ® 4000 System

K96K439

510(k) Notification

510(k) Summary Of Safety And Effectiveness Information Supporting A Substantially Equivalent Determination

OCT 18 1996

The following information presented in the Premarket Notification 510(k) for the CELL DYN® 4000 System constitutes data supporting a substantially-equivalent determination. Substantial equivalence is demonstrated between the CELL-DYN® 4000 System and the Abbott CELL-DYN 3500 Multi-Parameter Automated Hematology Analyzer, #K951496/S001 for the hemagram and white cell (WBC) differential parameters. Substantial equivalence is also demonstrated between the CELL-DYN® 4000 System and the Becton Dickinson FACScan™ Flow Cytometer ReticCOUNT™ Reticulocyte Enumeration Software, #K872166/A for reticulocytes. For enumeration of nucleated red blood cells (NRBCs) equivalence is demonstrated by comparison to the manual microscopic WBC differential count.

Intended Use: The CELL-DYN® 4000 System is a fully automated hematology analyzer intended for in-vitro diagnostic use in the clinical hematology laboratory of a hospital, medical clinic, or reference laboratory.

Device Description: The CELL-DYN® 4000 System has five main modules: the Analyzer, which aspirates, dilutes and analyzes each whole blood specimen; the Autoloader, which automatically identifies, mixes, and presents specimens for processing; the Pneumatic Unit, which controls fluid movement in the Analyzer and tube movement in the Autoloader; the Data Station, which controls all system processing and provides the primary operator interface with the system; and the Color Printer, which generates reports automatically or on demand.

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specimen and report the following hematological parameters:
White Blood Cell Parameters:	Red Blood Cell Parameters:
WBC -- White Blood Cell or leukocyte count	RBC -- Red Blood Cell or erythrocyte count
NEU -- Neutrophil absolute count	HCT -- Hematocrit
%N -- Neutrophil percent	MCV -- Mean Corpuscular Volume
LYM -- Lymphocyte absolute count	RDW -- Red Cell Distribution Width
%L -- Lymphocyte percent	NRBC -- Nucleated Red Blood Cell absolute count
MONO -- Monocyte absolute count	NR/W -- Nucleated Red Blood Cell percent of WBC count
%M -- Monocyte percent	Hemoglobin Parameters:
EOS -- Eosinophil absolute count	HGB -- Hemoglobin concentration
%E -- Eosinophil percent	MCH -- Mean Corpuscular Hemoglobin
BASO -- Basophil absolute count	MCHC -- Mean Corpuscular Hemoglobin Concentration
%B -- Basophil percent
*vWF -- Viable White Cell fraction
*BAND -- Band Neutrophil absolute count	Reticulocyte Parameters:
*%BD -- Band Neutrophil percent	RETC -- Reticulocyte concentration
*IMMG -- Immature Granulocyte absolute count	%R -- Reticulocyte percent of RBC count
*%IG -- Immature Granulocyte percent	*IRF -- Immature Reticulocyte Fraction
*BLST -- Blast absolute count	Platelet Parameters:
*%BL -- Blast percent	PLT -- Platelet Count
*VARL -- Variant Lymphocyte absolute count	MPV -- Mean Platelet Volume
*%VL -- Variant Lymphocyte percent	*PDW -- Platelet Distribution Width
	*PCT -- Plateletcrit

The CELL-DYN 4000 is designed to analyze EDTA-anticoagulated whole blood

These parameters are provided for laboratory use only and are not reportable in the US

Principles of Operation: The analyzer counts, sizes and classifies blood cells by the combination of flow cytometry methods: Laser Optical Scatter and Fluorescence, Focused Flow Impedance, and Absorption Spectrophotometry. The CELL-DYN® 4000 System uses an Argon-ion laser as the optical light source. The Optical Bench detects light in the form of scatter from blood cell surfaces and internal structures, or fluorescent light from specially stained blood cells.

For the WBC parameters and NRBCs, whole blood is diluted with a reagent containing a red fluorescent dye. Data are simultaneously collected for four angles (0°, 7°, 90°, and 90ºD) of scatter and red fluorescence (FL3) as each cell passes through the laser beam. NRBCs, identified by fluorescence, are excluded automatically from the WBC count. For the RBC and the PLT parameters, whole blood is diluted with a reagent that prepares the cells for measurement. The dilution is split and measured by both laser optical scatter (7° and 90°) and Focused Flow Impedance with Injection Metering.

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510(k) Notification

For the hemoglobin parameters, whole blood is diluted with a cyanide free reagent and the hemoglobin is measured optically by absorbance (540nm).

For the reticulocyte parameters, an aliquot of the RBC/PLT dilution is diluted with a reagent containing a green fluorescent dye. Data are collected for scatter (7º) and green fluorescence (FL1) as each cell passes through the laser beam.

Similarities and Differences: The CELL-DYN® 4000 System has similarities to one or more of the methods of determination for hemagram and automated WBCs differential parameters used by the following hematology analyzers: Coulter® Counters (Model ZBI, Hemoglobinometer, S-Plus Series and STKS); Sysmex™ NE Series; Technicon H*1™ Series; Becton Dickinson FACScan™, and Abbott CELL-DYN® 3000 Series. The CELL-DYN® 4000 System has similarities to one or more of the methods of determination for reticulocyte enumeration used by the Becton Dickinson FACScan™ and the Sysmex™ R-3000.

The Coulter® Counters (Model ZBI, S-Plus Series and STKS), Abbott CELL-DYN® 3000 Series, and the CELL-DYN® 4000 System are similar in that they use impedance for counting and sizing RBCs and PLTs. The CELL-DYN 4000 and the Sysmex™ NE series are similar in that they both use Focused Flow Impedance to count and size RBCs and PLTs. The Technicon H*1™ series and the CELL-DYN® 4000 System are similar in that they both use Injection Metering to measure RBCs and PLTs optically. The CELL DYN® 4000 System is different in that it counts RBCs and PLTs by both the optical and impedance methods and compares the data as an internal quality check. WBCs are counted and classified by the Abbott CELL-DYN® 3000 Series Systems and the CELL-DYN® 4000 System in a very similar manner using four simultaneously collected angles of laser light scatter. They are different in that the Abbott CELL-DYN® 3000 Series Systems use a helium neon laser, while the CELL-DYN® 4000 System uses an Argon-ion laser that allows fluorescent data to be collected simultaneously with the optical scatter data. This change enables the CELL-DYN 4000 to count and classify WBCs, NRBCs, and fragile (nonviable) WBCs. The Becton Dickinson FACScan™ and the CELL-DYN® 4000 System both use an Argon-ion laser. The FACScan is also capable of identifying NRBCs and non-viable WBCs. NRBCs are stained for enumeration by both the CELL-DYN® 4000 System and the manual microscopic differential.

The Becton Dickinson FACScan™, the Sysmex™ R-3000, and the CELL-DYN® 4000 System are similar in that they enumerate reticulocytes in EDT A-anticoagulated whole blood using optical laser scatter and fluorescence. They are different in that for the Becton Dickinson FACScan™, specimens are externally stained with Thiazol Orange an incubated for 90 minutes and then manually presented for measurement. For the Sysmex™ R-3000, specimens are automatically diluted and stained using Auromine Orange and then measured. The CELL-DYN® 4000 System is different in that it automatically dilutes the

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specimen with a fast acting proprietary dye which requires no incubation prior to measurement.

Equivalency Data: The data complied to support the claim that the CELL-DYN® 4000 System is substantially equivalent to the Abbott CELL-DYN® 3500 System includes accuracy, precision, linearity, and carryover.

The data supports the claim that the CELL-DYN® 4000 System is substantially equivalent to the Abbott CELL-DYN® 3500 System for the hemagram and automated WBC differential parameters and to the Becton Dickinson FACScan™ for the reticulocyte parameters. The accuracy, precision, and linearity data shows performance to manufacturer's specifications.

Conclusion: The CELL-DYN® 4000 System shows an evolution of the technologies used on one or more of the currently available analyzers to count, size, and classify whole blood cells and their related parameters, and more specifically to the technologies used on the Abbott CELL-DYN® 3500 System and the Becton Dickinson FACScan™.

The 510(k) Summary was prepared and submitted by:

Janice E. Brown Regulatory Affairs Manager Abbott Diagnostics 5440 Patrick Henry Drive Santa Clara, CA 95054

Phone: 408 567-3512 408 982-4863 Fax:

Regulation Number and Section

§ 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.”