COULTER STKS ANALYZER WITH CD4 & CD8 LYMPHOCYTE ANALYSIS

• K Number: K961278
• Device Name: COULTER STKS ANALYZER WITH CD4 & CD8 LYMPHOCYTE ANALYSIS
• Manufacturer: COULTER CORP.
• Date Cleared: 1996-07-22 ( 110 days)
• Product Code: GKZ
• Regulation Number: 864.5220
• Type: Traditional
• Panel: Hematology
• Reference & Predicate Devices: K922745 , K922744 , K885093 , K932030
• Predicate For: N/A

Intended Use

COULTER STKS Analyzer with CD4 and CD8 Lymphocyte Analysis is a complete system consisting of reagents, sample processing accessories, instrument and software. The system is intended "For In Vitro Diagnostic Use" to identify and enumerate CD4+ and CD8+ T lymphocyte percentages and absolute counts in whole blood using either of two versions of a quantitative, automated hematology analyzer and leukocyte differential counter: COULTER® STKS Analyzer or COULTER® STKS Analyzer with Reticulocyte Analysis. The system is also intended to provide the CD4/CD8 ratio, a complete blood count (CBC) and a white blood cell (WBC) differential. Reticulocyte percentage and absolute count are only available if using the COULTER® STKS Analyzer with Reticulocyte Analysis.

Device Description

COULTER® STKS Analyzer with CD4 and CD8 Lymphocyte Analysis is a complete system consisting of reagents, sample processing accessories, instrument and software.

AI/ML Overview

Here's a breakdown of the acceptance criteria and study details for the COULTER® STKS Analyzer with CD4 and CD8 Lymphocyte Analysis, based on the provided text:

Acceptance Criteria and Reported Device Performance

Acceptance Criteria Category	Specific Acceptance Criteria (Implied)	Reported Device Performance
Accuracy	Substantial equivalence to comparator method (CD3/CD4 and CD3/CD8 by Flow Cytometry) for CD4+ and CD8+ T lymphocyte percentages and absolute counts. Identification and enumeration of essentially identical numbers of lymphocytes.	Demonstrated that STKS with CD4 and CD8 Analysis and CD3/CD4 and CD3/CD8 by Flow Cytometry identify and enumerate essentially identical numbers of lymphocytes in whole blood specimens.
Linearity	Demonstrate linearity of assays across a range of CD4+ or CD8+ T lymphocyte concentrations.	Demonstrated linearity of the assays using regression analyses and 95% confidence intervals of recovered versus expected absolute counts.
Within Run (Intralaboratory) Precision	Demonstrate acceptable precision for CD4+ and CD8+ T lymphocyte concentrations on the same day.	Demonstrated within-run precision of the assays using means ± 1 SD and CVs.
Between Run (Run-to-Run) Precision	Demonstrate acceptable consistency between duplicate measurements on a STKS.	Demonstrated between-run precision of the assays using minimums, maximums, means, and mean differences between runs ± 1 SD.
Interlaboratory Precision	Demonstrate acceptable precision across different technicians and instruments for CD4+ and CD8+ T lymphocyte concentrations.	Demonstrated within-run (intralaboratory) precision of the assays using means ± 1 SD and CVs (Note: The text states "within run (intralaboratory) precision" for the interlaboratory section, which appears to be a typo or an overlap in the description as it should ideally reflect interlaboratory measures).

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Study Details

1. Sample Size Used for the Test Set and Data Provenance:

   • Sample Size: Not explicitly stated as a number. The study used "Normal and abnormal (i.e., HIV, organ transplant, cancer, autoimmune disease) whole blood specimens."
   • Data Provenance: Specimens were collected from a "geographically diverse population of males and females unselected as to race and ranging in age from 18 to 85 years." This indicates data from human subjects but does not specify a country. It is a prospective collection for the purpose of this study, as specimens were divided and processed specifically for the comparison.

2. Number of Experts Used to Establish the Ground Truth for the Test Set and the Qualifications of Those Experts:

   • Number of Experts: Not applicable. The "ground truth" and comparator method in this study are established laboratory techniques (flow cytometry using specific antibody reagents). The comparison is between two analytical methods, not dependent on expert visual review or judgment for establishing the reference.
   • Qualifications of Experts: N/A, as the ground truth is a technical measurement from a comparator device.

3. Adjudication Method for the Test Set:

   • Adjudication Method: Not applicable. The study compares quantitative measurements from two different instruments/methods. There is no human adjudication process involved in resolving discrepancies between interpretations, as it's a direct numerical comparison.

4. 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:

   • MRMC Study: No. This is a study comparing an automated hematology analyzer to a flow cytometer for lymphocyte analysis, not evaluating human reader performance with or without AI assistance. The device itself performs the analysis.

5. If a Standalone (i.e. algorithm only without human-in-the loop performance) Was Done:

   • Standalone Performance: Yes. The study directly assesses the performance of the COULTER® STKS Analyzer with CD4 and CD8 Lymphocyte Analysis (the subject device) by comparing its output (percentages and absolute counts) to a comparator method (flow cytometry). Both are automated analytical processes, and the performance described is that of the device itself.

6. The Type of Ground Truth Used (expert consensus, pathology, outcomes data, etc.):

   • Ground Truth Type: A comparator analytical method. The "ground truth" or reference standard for this study is the results obtained from CD3/CD4 and CD3/CD8 by Flow Cytometry using specified reagents (CD3(1gG1)-FITC/T4-RD1 or CD3(1gG1)-FITC/T8-RD1 on an EPICS XL-MCL or EPICS Profile II flow cytometer). This is a well-established and accepted method for lymphocyte immunophenotyping.

7. The Sample Size for the Training Set:

   • Sample Size: Not applicable. The provided document describes a performance validation study for a medical device (COULTER® STKS Analyzer) that uses predefined algorithms and reagents. There is no mention of machine learning or deep learning, and thus no "training set" in the computational sense. The device's algorithms would have been developed and validated internally by the manufacturer prior to this submission.

8. How the Ground Truth for the Training Set Was Established:

   • Ground Truth Establishment: Not applicable, as there is no "training set" for machine learning described. The device's internal algorithms are based on established principles of flow cytometry and hematology analysis.

Summary

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		JUL 22 1996
		K961278	Image: Coulter logo
COULTER CORPORATIONP.O. BOX 169015Miami, Florida 33116-9015 USA	Date:	April 1, 1996
Customer Service: [phone]Product Information: [phone](305) 380-3800(800) 327-6531	Title:	Summary of Safety and Effectiveness Information For 510(k) PremarketNotification
	Product:	COULTER® STKS Analyzer with CD4 and CD8 Lymphocyte Analysis
	Company:	Coulter Corporation11800 SW 147 AvenueMiami, FL 33196-2500
	Contact:	Dr. Marion S. Gaide (M/C: 31-B06)Senior Regulatory Affairs SpecialistCorporate Regulatory Affairs
	Telephone:	305-380-2594
	Common or Usual or Classification Name:	Lymphocyte Immunophenotyping UsingMonoclonal Antibody Reagents and AutomatedDifferential Cell Counters
	Product Classification:	Product Code: GKZ; C.F.R. Section: 864.5220; Classification Panel:Hematology and Pathology Devices; Device Class: II
	Intended Use:	COULTER STKS Analyzer with CD4 and CD8 Lymphocyte Analysis is acomplete system consisting of reagents, sample processing accessories,instrument and software. The system is intended "For In Vitro Diagnostic Use"to identify and enumerate CD4+ and CD8+ T lymphocyte percentages andabsolute counts in whole blood using either of two versions of a quantitative,automated hematology analyzer and leukocyte differential counter: COULTER®STKS Analyzer or COULTER® STKS Analyzer with Reticulocyte Analysis.The system is also intended to provide the CD4/CD8 ratio, a complete bloodcount (CBC) and a white blood cell (WBC) differential. Reticulocyte percentageand absolute count are only available if using the COULTER® STKS Analyzerwith Reticulocyte Analysis.
	Substantial Equivalence:	510(k) Premarket Notification: K922745CYTO-STAT®/COULTER CLONE® CD3(IgG1)-FITC/T4-RD1Monoclonal Antibody Reagent (CD3/CD4)
		510(k) Premarket Notification: K922744CYTO-STAT®/COULTER CLONE® CD3(IgG1)-FITC/T8-RD1Monoclonal Antibody Reagent (CD3/CD8)
		510(k) Premarket Notification: K885093COULTER® STKS Analyzer
		510(k) Premarket Notification: K932030COULTER® STKS Analyzer with Reticulocyte Analysis

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Product Differences: The subject hematologic method, STKS with CD4 and CD8 Analysis, and the comparator method, CD3/CD4 and CD3/CD8 by Flow Cytometry, necessarily differ in some respects as a result of the technologies used to achieve the same intended use. The primary differences are 1) instrumentation; 2) software versus reagent controls for lymphocyte gating and nontargeted monoclonal antibody binding to irrelevant cellular populations; 3) Mab conjugation; and 4) final product form of the reagents. With respect to instrumentation, it is noteworthy that the flow cytometric method requires both a flow cytometer and the same instrument used in the subject hematologic method.

Product Testing: Product testing to assess the performance of STKS with CD4 and CD8 Analysis is described below. Studies were designed in line with performance specifications and instructions for use provided in the product manuals and package inserts. Specimens were assayed with CD3/CD4 and CD3/CD8 by Flow Cytometry for comparison purposes. The results of product testing demonstrated that STKS with CD4 and CD8 Analysis met all performance specifications and provided CD4+ T lymphocyte values substantially equivalent to those obtained with the comparator method, CD3/CD4 and CD3/CD8 by Flow Cytometry.

1. Accuracy:

Normal and abnormal (i.e., HIV, organ transplant, cancer, autoimmune disease) whole blood specimens were collected from a geographically diverse population of males and females unselected as to race and ranging in age from 18 to 85 years. The specimens were divided and the samples processed and analyzed using either 1) COULTER™ CD4 or CD8 Cyto-Spheres™ Reagent on a STKS; or 2) CD3(1gG1)-FITC/T4-RD1 or CD3(1gG1)-FITC/T8-RD1 on an EPICS XL-MCL or EPICS Profile II flow ctyometer (gated on lymphocytes). A white blood cell count and 5-part differential were obtained for each whole blood specimen using the same STKS as in the subject hematologic method.

CD4+ and CD8+ T lymphocyte percentages and absolute counts obtained with CD4 and CD8 Cyto-Spheres Reagents on the STKS represented total CD4 and total CD8 values. Values obtained with CD3(lgG1)-FITC/T4-RD1 and CD3(IgG1)-FITC/T8-RD1 on the EPICS flow cytometers represented dual-positive, CD3+/CD4+ and CD3+/CD8+ values. Values were expressed in terms of percent of the total lymphocyte count and as absolute count (cells/uL). Flow cytometric values were corrected for lymphocyte purity (Lymphocyte Gate Limits: lymphocyte recovery ≥ 90%; lymphocyte purity ≥ 85%).

Results analyzed in terms of minimums, maximums, means ± 1 SD, regression and correlation analyses, and analyses of variance demonstrated that STKS with CD4 and CD8 Analysis and CD3/CD4 and CD3/CD8 by Flow Cytometry identify and enumerate essentially identical numbers of lymphocytes in whole blood specimens.

• 2. Linearity:
     Five replicate measurements were made at each of five individually prepared dilutions of a concentrated normal venous whole blood specimen to achieve a range of CD4+ or CD8+ T lymphocyte concentrations. Samples were processed with CD4 or CD8 Cyto-Spheres Reagent and analyzed on the STKS. Values were expressed in terms of absolute count (cells/uL).

Results analyzed in terms of regression analyses and 95% confidence intervals of the data points for recovered versus expected absolute counts (cells/yL) demonstrated linearity of the assays.

3. Within Run (Intralaboratory) Precision:

Ten replicate measurements were performed for each of CD4+ and CD8+ T lymphocyte concentrations on a STKS on the same day. A separate venous whole blood specimen was used for each CD4 or CD8 level and processed with CD4 or CD8 Cyto-Spheres Reagent prior to analysis. Values were expressed in terms of percent of the total lymphocyte count and as absolute count (cells/uL).

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Results analyzed in terms of means ± 1 SD and CVs demonstrated within run (intralaboratory) precision of the assays.

• 5. Between Run (Run-to-Run) Precision:
     Duplicate measurements were performed for CD4+ and CD8+ T lymphocyte concentrations on a STKS. A separate venous whole blood specimen was used to make both measurements. The specimen was divided and each half processed with CD4 or CD8 Cyto-Spheres Reagent prior to analysis. Values were expressed in terms of percent of the total lymphocyte count and as absolute count (cells/uL).

Results analyzed in terms of minimums, maximums, means, and mean differences between runs ± 1 SD demonstrated between run (run-to-run) precision of the assays.

Interlaboratory Precision: ર.

Studies were performed for each of three levels of CD4+ and CD8+ T lymphocyte concentrations on the same day by three technicians using three different STKS instruments. Replicate measurements were made on each STKS. The same venous whole blood specimen was used to make all replicate measurements on all three instruments for a particular CD4 or CD8 percentage or absolute count level. The specimen was divided into thirds and each third processed with CD4 or CD8 Cyto-Spheres Reagent prior to analysis. Values were expressed in terms of percent of the total lymphocyte count and as absolute count (cells/uL).

Results analyzed in terms of means ± 1 SD and CVs demonstrated within run (intralaboratory) precision of the assays.

Marion S. Gracie

Marion S. Gaide, Ph.D. Senior Regulatory Affairs Specialist Corporate Regulatory Affairs

April 1, 1896
Date

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.”