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.

Device Description

AI/ML Overview

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.

Summary

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FEB 1 0 2005

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Summary of Safety and Effectiveness for Section 1 D: COULTER® LH 750 Hematology Analyzer

General Information 1.0

Device Generic Name(s):	Automated differential cell counter
Device Trade Name(s):	COULTER® LH 750 Hematology Analyzer
Device Classification:	The COULTER® LH 750 Hematology Analyzer is a Class II medicaldevice.
Applicant Name and Address:	Beckman Coulter, Inc.Cellular Analysis Division11800 SW 147 AvenueMiami, FL 33196-2500

Date:

January 10, 2005

Legally Marketed Device(s) 2.0

The modified COULTER® LH 750 Hematology Analyzer claims substantial equivalence to the previously cleared COULTER® LH 750 Body Fluids Application.

FDA 510(k) Number(s): K030606

3.0 Device Description

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. The following reagents, with 510(k) numbers indicated where applicable, are qualified for use on the COULTER LH 750 Hematology Analyzer with Version 2B (or higher) software:

· 5C® Cell Control (K781969) and COULTER RETIC-C™ Cell control (K930119) hematology quality control materials used to monitor the instrument performance. COULTER® LIN-C® linearity control (K955334) verifies reportable range of the CBC parameters.
· COULTER® LH 700 SERIES or ISOTON 4 Diluent. Intended for use as a diluent for counting and sizing blood cells on COULTER® LH 700 SERIES hematology analyzers.
· COULTER Lyse S® III diff or Lyse S® 4. Intended for the simultaneous quantitative determination of hemoglobin and for leukocyte counting and sizing on COULTER® hematology analyzers.
· COULTER CLENZ® cleaning agent to prevent protein buildup on surfaces.
· COULTER Latron™ Primer and Latron Control (K885028) to monitor VCS performance.

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· COULTER LH 700 SERIES Pak, containing Erythrolyse™ tytic reagent and Stabilyse™ to oooe fer Er. Er. roe State to allow differentiation into subpopulations.
· COULTER LH 700 SERIES RETIC Pak, containing Reagent A and Reagent B, is used for clearing red cells and staining reticulocytes.
COULTER S-CAL® Hematology Calibrator (K840794), alternative to whole blood reference method of calibration. Intended for use in ensuring accurate instrument measurements.

Principle of Method: 4.0

The COULTER LH 750 Hematology Analyzers utilizes the Coulter Principle for enumerating and sizing blood cells, automatic diluting and mixing for sample processing and a single beam Sizing blood oche, actornatio and ... They use COULTER VCS (yolume, conductivity, light scatter) technology for WBC Differential analysis and classification and reticulocyte analysis. The analyzers use a reagent system consisting of an isotonic diluent, lytic reagents to lyse the red cells without significantly affecting the white cells and an instrument cleaner. Additionally, all systems include reagents used for reticulocyte staining and analysis.

For body fluids analysis, specimen is aspirated into the LH 700 Series Analyzer via the manual mode and is diluted in separate WBC and RBC baths. The Coulter Method of counting cells is used to detect and measure changes in electrical resistance when a cell, suspended in a conductive diluent, passes through a small aperture. Each suspended cell acts as an insulator. As the cell passes through the aperture, it momentarily increases the resistance of the electrical path between two submerged electrodes, one located on each side of the aperture. The resistance botwoon the cabrical pulse. The accumulation of electrical pulses are channelized, processed for coincidence correction, and multiplied by a calibration factor, yielding the WBC and RBC counts.

The WBC result represents the TNC (total nucleated cell count) in the analysis of Body Fluids.

5.0 Indications for Use:

Description of the modification: 6.0

The labeling for the marketed COULTER LH 750 hematology analyzer with Version 2B software release will be modified relative to draft product labeling submitted in the original premarket notification (K030606) 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.

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Image /page/2/Picture/0 description: The image shows the logo for the Department of Health & Human Services - USA. The logo consists of a circular seal with the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" arranged around the perimeter. Inside the circle is an abstract symbol resembling an eagle or bird in flight, composed of three stylized wing shapes.

DEPARTMENT OF HEALTH & HUMAN SERVICES

Stan Sugrue, Ph.D. Senior Regulatory Affairs Specialist Premarket Product Regulatory Compliance Beckman Coulter, Inc. 11800 SW 147 Avenue Miami, Florida 33196-2500

FEB 1 0 2005

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

K050057 Re:

Trade/Device Name: COULTER® LH 750 Hematology Analyzer Body Fluids Application Regulation Number: 21 CFR § 864.5220 Regulation Name: Automated differential cell counter Regulatory Class: II Product Code: GKZ Dated: January 10, 2005 Received: January 11, 2005

Dear Dr. Sugrue:

We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and 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) that do not require approval of a premarket approval application (PMA). 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 (PMA), it may be subject to such additional controls. Existing major regulations affecting your device can be found in Title 21, Code of Federal Regulations (CFR), Parts 800 to 895. In addition, FDA may publish further announcements concerning your device in the Federal Register.

Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Parts 801 and 809); and good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820). This letter will allow you to begin marketing your device as described in your Section 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.

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If you desire specific information about the application of labeling requirements to your device, n you stions on the promotion and advertising of your device, please contact the Office of In Vitro Diagnostic Device Evaluation and Safety at (240) 276-0484. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR Part 807.97). You may obtain other general information on your responsibilities under the Act from the Division of Small Manufacturers, International and Consumer Assistance at its toll-free number (800) 638-2041 or (301) 443-6597 or at its Internet address http://www.fda.gov/cdrh/industry/support/index.html

Sincerely yours,

lobatz Beckerh

Robert L. Becker, Jr., MD, PK.D Director Division of Immunology and Hematology Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health

Enclosure

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Section 1C:

INDICATIONS FOR USE

K05005 Not assigned 510(k) Number (if known):

COULTER® LH 750 Body Fluids Application Device:

Intended Use:

The LH 700 Series Body Fluid Application is a procedure for obtaining in vitro The EN 700 Geterminations of leukocytes (WBC) and erythrocytes (RBC) in quantitative determinations of Barbovial fluid, using a COULTER LH 700 Series Hematology Analyzer.

21 CFR 864.5220 Automated differential cell counter

An automated differential cell counter is a device used to identify and classify one or more of the formed elements of blood.

Prescription Use X

Over-The-Counter Use

(Per 21 CFR 801.109)

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

Concurrence of CDRH, Office of Device Evaluation (ODE)

Josephine Bautista

Division Sign-off

Office of In Vitro Diagnostic Device Evaluation and Safety

510(k) K050057

LH 750- Synovial Fluid Sample Stability Special 510k

Beckman Coulter, Inc.

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.”