The COULTER® Z2 instrument may be used for in vitro diagnostic use to determine the human erythrocyte concentration (Red Cell Count or RBC), leukocyte concentration (White Cell Count or WBC) and thrombocyte concentration (Platelet Count or Plt). In addition, the COULTER Z2 also provides the mean erythrocyte volume (Mean Cell Volume or MCV) and the mean thrombocyte volume (Mean Platelet Volume or MPV).

Device Description

The COULTER Z2 is a general purpose dual threshold particle counter and sizer designed to count and size particles, suspended in an aqueous electrolyte solution, within the range of 1 to 120 um equivalent spherical diameter. The instrument is designed for both biological and industrial use. As with the predicate devices, the COULTER Z2 utilizes the Coulter principle for the enumeration and sizing of blood cells. The same reagent system, composed of an isotonic diluent, lytic reagent to lyse red blood cells for WBC measurement and instrument cleaner, is used on COULTER STKS, Z1, and Z2 instruments. The COULTER STKS, Z1, and Z2 instruments are capable of determining the human erythrocyte concentration (Red Cell Count or RBC), leukocyte concentration (White Cell Count or WBC) and thrombocyte concentration (Platelet Count or Plt). In addition, like the COULTER STKS, the COULTER Z2 also provides the mean erythrocyte volume (Mean Cell Volume or MCV) and the mean thrombocyte volume (Mean Platelet Volume or MPV). Both the COULTER Z1 and the Z2 instruments contain a hydraulic metering station built into the electronics main unit, measure a restricted range of particle sizes (within the range 1 to 120 µM) and utilize surface-mount technology. Operator-adjustable controls are accessible by means of a keyboard data terminal.

AI/ML Overview

Here's a breakdown of the acceptance criteria and study information for the COULTER® Z2 Analyzer, based on the provided text:

Acceptance Criteria and Device Performance for COULTER® Z2 Analyzer

The provided document describes the COULTER® Z2 Analyzer and its substantial equivalence to predicate devices, focusing on the added parameters of Mean Cell Volume (MCV) and Mean Platelet Volume (MPV). The "acceptance criteria" are implicitly defined by the reported performance metrics (imprecision and accuracy) that demonstrate its equivalence to already commercially distributed hematology analyzers.

1. Table of Acceptance Criteria and Reported Device Performance

Since explicit "acceptance criteria" are not given in numerical ranges (e.g., "CV% must be <= X"), the table below reflects the reported performance data from the "Summary of Performance Data" section, implying these values met the necessary standards for substantial equivalence. The predicate device performance is not explicitly detailed in the provided text for a direct comparison in terms of numerical criteria, but the study asserts "substantial equivalence" through these results.

PARAMETER	UNITS	Performance Metric	Reported Value
Imprecision Analysis (Reproducibility)
RBC	X 10^6 cells/µL	Mean	4.77
RBC	X 10^6 cells/µL	SD	0.0981
RBC	X 10^6 cells/µL	CV%	2.06
PLT	x 10^3 cells/µL	Mean	153.8
PLT	x 10^3 cells/µL	SD	4.54
PLT	x 10^3 cells/µL	CV%	2.95
MPV	fL	Mean	7.99
MPV	fL	SD	0.12
MPV	fL	CV%	1.48
MCV	fL	Mean	83.14
MCV	fL	SD	0.73
MCV	fL	CV%	0.87
Accuracy Analysis (Compared Samples)
RBC	x 10^6 cells/µL	N	31
RBC	x 10^6 cells/µL	Pop. Min	3.50
RBC	x 10^6 cells/µL	Pop. Max	6.02
RBC	x 10^6 cells/µL	Mean Diff.	0.16
RBC	x 10^6 cells/µL	SD	0.24
RBC	x 10^6 cells/µL	Mean % Diff	3.51
RBC	x 10^6 cells/µL	Corr Coeff	0.90
MCV	fL	N	31
MCV	fL	Pop. Min	78.00
MCV	fL	Pop. Max	97.46
MCV	fL	Mean Diff.	0.54
MCV	fL	SD	2.7
MCV	fL	Mean % Diff	0.65
MCV	fL	Corr Coeff	0.82
PLT	x 10^3 cells/µL	N	31
PLT	x 10^3 cells/µL	Pop. Min	134
PLT	x 10^3 cells/µL	Pop. Max	483
PLT	x 10^3 cells/µL	Mean Diff.	56.23
PLT	x 10^3 cells/µL	SD	50.09
PLT	x 10^3 cells/µL	Mean % Diff	23.13
PLT	x 10^3 cells/µL	Corr Coeff	0.82
MPV	FL	N	31
MPV	FL	Pop. Min	7.15
MPV	FL	Pop. Max	11.27
MPV	FL	Mean Diff.	0.55
MPV	FL	SD	0.43
MPV	FL	Mean % Diff	6.52
MPV	FL	Corr Coeff	0.89

2. Sample Size Used for the Test Set and Data Provenance

Sample Size for Test Set:
- For Reproducibility (Imprecision) analysis: The table for "COULTER Z2 Analyzer Imprecision Analysis by Reproducibility" does not explicitly state the number of samples or runs, but presents mean, SD, and CV% data, typically derived from multiple measurements on a set of samples.
- For Accuracy analysis (Compared Samples): N = 31 samples.
Data Provenance: The document does not specify the country of origin of the data or whether the study was retrospective or prospective. It is a submission to the US FDA, so it is likely US-based, but this is not explicitly stated.

3. Number of Experts Used to Establish the Ground Truth for the Test Set and Their Qualifications

The document does not mention the use of experts or their qualifications for establishing ground truth for the test set. The study focuses on comparing the device's results to a reference method, which is implicitly the predicate device or a recognized standard for cell counting.

4. Adjudication Method for the Test Set

The document does not describe any adjudication method. This type of study (hematology analyzer performance) typically relies on direct comparison to reference methods or predicate devices rather than expert adjudication.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was done

No, a Multi-Reader Multi-Case (MRMC) comparative effectiveness study was not done. This study is for an automated cell counter, not an interpretative diagnostic aid for human readers. Therefore, the concept of "how much human readers improve with AI vs without AI assistance" is not applicable here.

6. If a Standalone (algorithm only without human-in-the-loop performance) was done

Yes, the study describes the standalone performance of the COULTER® Z2 Analyzer. The data presented for imprecision and accuracy are measurements directly from the device, without human intervention in the result generation or interpretation to modify the output. The device itself is described as "semi-automated," implying some human interaction for sample loading and operation, but the performance data presented are inherent to the device's measurement capabilities.

7. The Type of Ground Truth Used

The "ground truth" for this study appears to be established by comparison to the predicate devices (COULTER® Z1 and COULTER® STKS analyzers) and/or a reference method or standard laboratory measurements. The summary states, "Equivalence is demonstrated through compared sample accuracy and imprecision results," implying that the Z2's measurements were compared against established, acceptable values, likely from the predicate devices which were already cleared. The specific "ground truth" (e.g., gold standard manual counting, another validated automated system) for the compared samples is not explicitly detailed beyond being "compared samples."

8. The Sample Size for the Training Set

The document does not specify a separate "training set" or its sample size. This is common for medical devices approved through the 510(k) pathway, especially for analytical devices where performance is characterized through reproducibility and accuracy against predicate devices or reference methods, rather than machine learning model training.

9. How the Ground Truth for the Training Set Was Established

Since no explicit training set is mentioned in the context of machine learning, there is no description of how ground truth for a training set was established. The performance evaluation focuses on the device's analytical capabilities through direct measurement and comparison.

Summary

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Summary of Safety and Effectiveness

COULTER® Z2 Analyzer

Submitted By: 1.0

Tom English Manager, Premarket Product Regulatory Compliance Coulter Corporation 11800 SW 147 Avenue, MC 31-B06 Miami, FL 33196 Telephone: (305) 380-4331 FAX: (305) 380-3618

2.0 Date Submitted:

March 30, 1999

3.0 Device Names:

3.1 Proprietary Name(s):
COULTER® Z2 Analyzer
3.2. Classification Name(s):
Automated cell counter (21 CFR §864.5200)

Predicate Device(s): 4.0

COULTER® Z1 Analyzer COULTER® STKS Analyzer

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5.0 Description

COULTER Z2 has the same technological characteristics and is substantially equivalent to the COULTER® STKS analyzer that was cleared by 510(k) K885093 cleared on Dec. 28, 1988.

The COULTER Z2 is the same device as the COULTER® Z1, cleared by 510(k) K952308 on October 6, 1995 except for the measurement of two additional parameters, Mean Cell Volume (MCV) and Mean Platelet Volume (MPV) and the ability to provide the operator with on-screen/printed graphs of channelized size distribution data.

As with the predicate devices, the COULTER Z2 utilizes the Coulter principle for the enumeration and sizing of blood cells. The same reagent system, composed of an isotonic diluent, lytic reagent to lyse red blood cells for WBC measurement and instrument cleaner, is used on COULTER STKS, Z1, and Z2 instruments.

The COULTER STKS, Z1, and Z2 instruments are capable of determining the human erythrocyte concentration (Red Cell Count or RBC), leukocyte concentration (White Cell Count or WBC) and thrombocyte concentration (Platelet Count or Plt). In addition, like the COULTER STKS, the COULTER Z2 also provides the mean erythrocyte volume (Mean Cell Volume or MCV) and the mean thrombocyte volume (Mean Platelet Volume or MPV).

Both the COULTER Z1 and the Z2 instruments contain a hydraulic metering station built into the electronics main unit, measure a restricted range of particle

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sizes (within the range 1 to 120 µM) and utilize surface-mount technology. Operator-adjustable controls are accessible by means of a keyboard data terminal.

6.0. Intended use:

The COULTER® Z Series Analyzers is a semi-automated device that may be used for in vitro diagnostic use to determine the human erythrocyte concentration (Red Cell Count or RBC), leukocyte concentration (White Cell Count or WBC) and thrombocyte concentration (Platelet Count or Pit). In addition, the COULTER Z2 also provides the mean erythrocyte volume (Mean Cell Volume or MCV) and the mean thrombocyte volume (Mean Platelet Volume or MPV).

This submission provides information concerning the safety and effectiveness principally of the two parameters added to the instrument.

7.0 Comparison to Predicate(s):

The following tables outline the basic similarities and differences between the Z2 and the predicate devices.

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SIMILARITIES to the PREDICATES

COULTER® Z2	COULTER® Z1	COULTER® STKS
Utilizes the Coulter principle for enumerationand sizing of blood cells.	Utilizes the Coulter principle for enumerationand sizing of blood cells.	Utilizes the Coulter principle for enumerationand sizing of blood cells.
Reagent system includes an isotonic diluent,lytic reagent and instrument cleaner.	Reagent system includes an isotonic diluent,lytic reagent and instrument cleaner.	Reagent system includes an isotonic diluent,lytic reagent and instrument cleaner.
Ability to print sample results.	Ability to print sample results.	Ability to print sample results.
Uses coincidence correction. The frequencyof coincidence is a statistically predictablefunction of particle concentration and iscorrected by the instrument.	Uses coincidence correction. The frequencyof coincidence is a statistically predictablefunction of particle concentration and iscorrected by the instrument.	Uses coincidence correction. The frequencyof coincidence is a statistically predictablefunction of particle concentration and iscorrected by the instrument.
The ability to provide the operator with on-screen/printed graphs of channelized sizedistribution data.	See DIFFERENCES table	The ability to provide the operator with on-screen/printed graphs of channelized sizedistribution data.
Separate measurement of RBC, WBC and PLTis required.	Separate measurement of RBC, WBC and PLTis required.	See DIFFERENCES table
Uses a single aperture each for WBC andRBC counting and sizing.	Uses a single aperture each for WBC andRBC counting and sizing.	See DIFFERENCES table
No ability to store data.	No ability to store data.	See DIFFERENCES table
Automated Calibration calculation but operatorintervention required for Control calculations.	Automated Calibration calculation but operatorintervention required for Control calculations.	See DIFFERENCES table
Sample probe requires manually cleaning	Sample probe requires manually cleaning	See DIFFERENCES table
Uses detachable keypad for operatorinterface.	Uses detachable keypad for operatorinterface.	See DIFFERENCES table.
System does not measure hemoglobin	System does not measure hemoglobin	See DIFFERENCES table
Requires external dilutor to supply the propervolume of diluent for predilute samples.	Requires external dilutor to supply the propervolume of diluent for predilute samples.	See DIFFERENCES table

COULTER® Z2	COULTER® Z1	COULTER® STKS
Can be used For In Vitro Diagnostic Use forRed Blood Cell Count (RBC), White Blood CellCount (RBC), Platelet (Plt), Mean Cell Volume(MCV), Mean Platelet Volume (MPV).	Can be used For In Vitro Diagnostic Use forRed Blood Cell Count (RBC), White Blood CellCount(WBC), Platelet (Plt),. Does not measureMean Cell Volume (MCV), Mean PlateletVolume.	Can be used For In Vitro Diagnostic Use forRed Blood Cell Count (RBC), White Blood CellCount (WBC), Platelet (Plt), Mean Cell Volume(MCV), Mean Platelet Volume (MPV). Otherparameters include a five-part leukocytedifferential count, hemoglobin, hematocrit,mean cell hemoglobin, mean cell hemoglobinconcentration and red cell distribution width.See SIMILARITIES table
The ability to provide the operator with on-screen/printed graphs of channelized sizedistribution data.	No channelizing capability	See SIMILARITIES table
Manual dilution of blood samples.	See SIMILARITIES table	Automated dilution of blood samples.
Uses a single aperture each for WBC and RBCcounting and sizing.	See SIMILARITIES table	Uses three apertures each for WBC and RBCcounting and sizing.
System does not measure hemoglobin	See SIMILARITIES table	The system uses the lysed WBC dilution tomeasure Hgb in the WBC bath. A beam ofincandescent light passes through the WBCbath and then through a 525-nm optical filterand is measured by a photodiode.
No ability to store data.	See SIMILARITIES table	Ability to store data.
Requires external dilutor to supply the propervolume of diluent for predilute samples.	See SIMILARITIES table	Ability to dispense the proper volume of diluentfor predilute samples.
Automated Calibration calculation but operatorintervention required for Control calculations.	See SIMILARITIES table	Automated Calibration and Controlcalculations.
Uses detachable keypad for operator interface.	See SIMILARITIES table	Uses Universal Icons for operator interface.
Sample probe requires manually cleaning	See SIMILARITIES table	Automated, self-cleaning probe.
Separate mesurement of RBC, WBC and PLTis required.	See SIMILARITIES table	Simultaneous measurement of all parameters.

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DIFFERENCES from the PREDICATES

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8.0 Summary of Performance Data:

The data in the Premarket Notification on safety and effectiveness supports a finding of substantial equivalence to hematology analyzers already in commercial distribution. Equivalence is demonstrated through compared sample accuracy and imprecision results.

PARAMETER	UNITS	MEAN	SD	CV%
RBC	X 106 cells/µL	4.77	.0981	2.06
PLT	x 103 cells/µL	153.8	4.54	2.95
MPV	fL	7.99	0.12	1.48
MCV	fL	83.14	0.73	0.87

COULTER Z2 Analyzer Imprecision Analysis by Reproducibility

COULTER Z2 Analyzer ACCURACY ANALYSIS: COMPARED SAMPLES

PARAMETER	UNITS	N	POP.MIN	POP.MAX	MEANDIFF.	SD	MEAN%DIFF	CORRCOEFF
RBC	x 106cells/µL	31	3.50	6.02	0.16	0.24	3.51	0.90
MCV	fL	31	78.00	97.46	0.54	2.7	0.65	0.82
PLT	x 103cells/µL	31	134	483	56.23	50.09	23.13	0.82
MPV	FL	31	7.15	11.27	0.55	0.43	6.52	0.89

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Image /page/6/Picture/1 description: The image shows the logo for the Department of Health & Human Services (HHS). The logo features a stylized abstract image of an eagle or bird with three curved lines representing its wings or feathers. The text "DEPARTMENT OF HEALTH & HUMAN SERVICES 'USA'" is arranged in a circular fashion around the bird image.

MAY 1 1 1999

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

Mr. Thomas J. English Manager, Premarket Product Regulatory Compliance Coulter Corporation 11800 SW 147 Avenue, MC 31-B06 Miami, Florida 33196

Re: K991070 Trade Name: COULTER® Z2 Analyzer Regulatory Class: II Product Code: GKL Dated: March 30, 1999 Received: March 31, 1999

Dear Mr. English:

We have reviewed your Section 510(k) notification of intent to market the device referenced above and we have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food, Drug, and Cosmetic Act (Act). You may, therefore, market the device, subject to the general controls provisions of the Act. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration.

If your device is classified (see above) into either class II (Special Controls) or class III (Premarket Approval), it may be subject to such additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 895. A substantially equivalent determination assumes compliance with the Current Good Manufacturing Practice requirements, as set forth in the Quality System Regulation (QS) for Medical Devices: General regulation (21 CFR Part 820) and that, through periodic QS inspections, the Food and Drug Administration (FDA) will verify such assumptions. Failure to comply with the GMP regulation may result in regulatory action. In addition, FDA may publish further announcements concerning your device in the Federal Register. Please note: this response to your premarket notification submission does not affect any obligation you might have under sections 531 through 542 of the Act for devices under the Electronic Product Radiation Control provisions, or other Federal laws or regulations.

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Page 2

Under the Clinical Laboratory Improvement Amendments of 1988 (CLIA-88), this device may require a CLIA complexity categorization. To determine if it does, you should contact the Centers for Disease Control and Prevention (CDC) at (770) 488-7655.

This letter will allow you to begin marketing your device as described in your 510(k) premarket notification. The FDA finding of substantial equivalence of your device to a legally marketed predicate device results in a classification for your device and thus, permits your device to proceed to the market.

If you desire specific advice for your device on our labeling regulation (21 CFR Part 801 and additionally 809.10 for in vitro diagnostic devices), please contact the Office of Compliance at (301) 594-4588. Additionally, for questions on the promotion and advertising of your device, please contact the Office of Compliance at (301) 594-4639. Also, please note the regulation entitled, "Misbranding by reference to premarket notification"(21 CFR 807.97). Other general information on your responsibilities under the Act may be obtained from the Division of Small Manufacturers Assistance at its toll-free number (800) 638-2041 or (301) 443-6597, or at its internet address "http://www.fda.gov/cdrh/dsma/dsmamain.html".

Sincerely yours,

Steven Dutman

Steven I. Gutman, M.D, M.B.A. Director Division of Clinical Laboratory Devices Office of Device Evaluation Center for Devices and Radiological Health

Enclosure

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INTENDED USE STATEMENT

K991070

FO BE ASSIGNED 510(k) Number (if known):

Device Name: COULTER® Z2 Analyzer

Intended Use:

21 CFR 864.5200 Automated cell counter

An automated cell counter is a fully-automated or semi-automated device used to count red blood cells, white blood cells, or blood platelets using a sample of the patients peripheral blood (blood circulating in one of the body's extremities, such as the arm). These devices may also measure hemoglobin or hematocrit and may also calculate or measure one or more of the red cell indices (the erythrocyte mean corpuscular volume, the mean corpuscular hemoglobin, or the mean corpuscular hemoglobin concentration). These devices may use either an electronic particle counting method or an optical counting method.

(PLEASE DO NOT WRITE BELOW THIS LINE-CONTINUE ON ANOTHER PAGE IF NEEDED)

Concurrence of CDRH, Office of Device Evaluation (ODE)

Peter E. Malins

Division Sign-Off) Division of Clinical Laboratory De 510(k) Number

Prescription Use
(Per 21 CFR 801.109)

Over-The-Counter Use

(Optional Form 1-2-96)

Regulation Number and Section

§ 864.5200 Automated cell counter.

(a)
Identification. An automated cell counter is a fully-automated or semi-automated device used to count red blood cells, white blood cells, or blood platelets using a sample of the patient's peripheral blood (blood circulating in one of the body's extremities, such as the arm). These devices may also measure hemoglobin or hematocrit and may also calculate or measure one or more of the red cell indices (the erythrocyte mean corpuscular volume, the mean corpuscular hemoglobin, or the mean corpuscular hemoglobin concentration). These devices may use either an electronic particle counting method or an optical counting method.(b)
Classification. Class II (performance standards).