IMMUNO-TROL™ Control Cells (Immuno-Trol) is an for an assayed, lysable whole blood quality control product for immunophenotyping analysis using monoclonal antibody reagents and flow cytomerry. It provides a positive cell control that is processed in the same manner as a whole blood sample. This allows verification of reagent performance and the methods used for staining targeted cells, lysing erythrocytes, and analyzing samples by flow cytometry. CD populations intended "For In Vitro Diagnostic Use" and those intended "For Research Use In Diagnostic Procedures." are given in separate tables in the TABLE OF EXPECTED RESULTS section of the Immuno-Trol package insert.

Immunophenotyping analysis by flow cytometry involves the identification and enumeration of targeted cells in whole blood samples. Whole blood samples are stained with monoclonal antibodies and erythrocytes are lysed prior to flow cytometric analysis. A positive cell control is required to verify reagent performance, sample performance, sample preparation methods, and staining procedures. A positive cell control should mimic a representative whole blood sample in terms of monoclonal antibody performance, erythrocyte lysing, and flow cytometric analysis.

Device Description

IMMUNO-TROL™ Control Cells (Immuno-Trol) is an assayed, lysable whole blood quality control product for immunophenotyping analysis using monoclonal antibody reagents and flow cytometry. It provides a positive cell control that is processed in the same manner as a whole blood sample.

AI/ML Overview

The IMMUNO-TROL™ Control Cells device is a quality control product for immunophenotyping analysis using monoclonal antibody reagents and flow cytometry. It is intended to provide a positive cell control that mimics a whole blood sample to verify reagent performance, sample preparation methods, and staining procedures.

Here's a breakdown of the acceptance criteria and supporting study details:

1. Acceptance Criteria and Reported Device Performance

The general acceptance criterion across all studies was that "all values met the Acceptance Criteria." While specific numerical performance targets (e.g., specific ranges for percent positive or absolute counts) are not explicitly stated in this document for each individual parameter, the document consistently indicates successful performance against these internal criteria. The comparison to predicate devices (Normal Whole Blood (NWB) and CYTO-TROL™ Control Cells Kit (CYTO-TROL)) served as an implicit benchmark for acceptable performance.

Performance Characteristic	Acceptance Criteria	Reported Device Performance
Vial-to-Vial Reproducibility	Consistency and reproducibility of Immuno-Trol filled vials, expressed in cells/mL. (Implicit: Values for RBC and WBC concentrations should fall within predefined acceptable ranges).	"The study results were expressed in terms of cells/mL and all values met the Acceptance Criteria. These data demonstrate the consistency and reproducibility of Immuno-Trol filled vials."
Lot-to-Lot Reproducibility	Consistency and reproducibility of Immuno-Trol between lots, expressed in percent positive (%) and absolute count (cells/uL) for leukocyte surface antigens. (Implicit: Values should fall within predefined acceptable ranges and demonstrate consistency across lots).	"Testing produced overall percent positive (%) and absolute count (as applicable) results for the leukocyte surface antigens given in the Immuno-Trol Package Insert. The study results were expressed in terms of percent positive (%) and absolute count (cells/uL) and all values met the Acceptance Criteria. These data demonstrate the consistency and reproducibility of Immuno-Trol between lots."
Stability (Closed Vial)	Immuno-Trol meets reagent and sample stability characteristics and claims for 90 days at 2-8°C, expressed in percent positive (%) and absolute count (cells/uL). (Implicit: Values should remain within predefined acceptable ranges over the specified duration and temperature).	"The study results were expressed in terms of percent positive (%) and absolute count (cells/uL) and all values met the Acceptance Criteria. These data demonstrate Immuno-Trol meets both reagent and sample stability characteristics and claims under the storage and temperature conditions studied."
Stability (Open Vial)	Immuno-Trol meets reagent and sample stability characteristics and claims for 30 days at 2-8°C, expressed in percent positive (%) and absolute count (cells/uL). (Implicit: Values should remain within predefined acceptable ranges over the specified duration and temperature).	"The study results were expressed in terms of percent positive (%) and absolute count (cells/uL) and all values met the Acceptance Criteria. These data demonstrate Immuno-Trol meets both reagent and sample stability characteristics and claims under the storage and temperature conditions studied."
Stability (Stored Prepared Sample)	Immuno-Trol meets reagent and sample stability characteristics and claims for 2 hours at 20-25°C and 24 hours at 2-8°C, expressed in percent positive (%) and absolute count (cells/uL). (Implicit: Values should remain within predefined acceptable ranges over the specified durations and temperatures).	"The study results were expressed in terms of percent positive (%) and absolute count (cells/uL) and all values met the Acceptance Criteria. These data demonstrate Immuno-Trol meets both reagent and sample stability characteristics and claims under the storage and temperature conditions studied."
Absolute Count Method Verification	Suitability of using the Flow-Count (Direct) Method for absolute count determination of Immuno-Trol leukocyte surface antigens. Absolute count results from Flow-Count (Direct) Method and Standard (Indirect) Method should be essentially identical and all values should meet acceptance criteria. (Implicit: Values should fall within predefined acceptable ranges and show equivalence between methods).	"The study results were expressed in terms of percent positive (%) and absolute count (cells/uL) and all values met the Acceptance Criteria. In addition, both the Flow-Count (Direct) Method and the Standard (Indirect) Method provided essentially identical absolute count results for Immuno-Trol and NWB. These data clearly demonstrate the suitability of using the Flow-Count (Direct) Method for absolute count determination of Immuno-Trol leukocyte surface antigens."
Assay Precision	Reproducibility of Immuno-Trol performance, with individual and combined assay precision for various study parameters meeting acceptance criteria. Performance should be comparable to NWB and CYTO-TROL with minimal variation (means, standard deviations, and coefficients of variation). (Implicit: Values should fall within predefined acceptable ranges and demonstrate similar precision to predicate devices).	"All values met the Acceptance Criteria. In addition, Immuno-Trol, NWB and CYTO-TROL varied little as evidenced by the means, standard deviations and coefficients of variation for the different sets of measurements. These data demonstrate Immuno-Trol performs in a manner comparable to the Predicate System components, NWB and CYTO-TROL."

Study Details

The provided document describes various studies conducted to assess the performance of IMMUNO-TROL™ Control Cells.

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

Vial-to-Vial Reproducibility: "The filled vials were sampled from Immuno-Trol lots at regular intervals across the fill." (Specific number of vials/samples, country of origin, and whether retrospective/prospective are not explicitly provided. However, the description implies prospective testing of manufactured lots.)
Lot-to-Lot Reproducibility: "Testing produced overall percent positive (%) and absolute count (as applicable) results for the leukocyte surface antigens given in the Immuno-Trol Package Insert." (Specific number of lots, different instrument-operator combinations, country of origin, and whether retrospective/prospective are not explicitly provided. Implies prospective testing.)
Stability Studies: Two study protocols were used: "Closed Vial: 90 days at 2-8℃; Open Vial: 30 days at 2-8℃" and "Stored Prepared Sample: 2 hours at 20-25°C; 24 hours at 2-8°C." "Immuno-Trol was tested using one-color, threecolor and four-color monoclonal antibody reagents under the different storage and temperature conditions over test periods extending up to and beyond the respective 90-day and 30-day claims." (Specific number of samples/lots, country of origin, and whether retrospective/prospective are not explicitly provided. Implies prospective testing over time.)
Absolute Count Method Verification: "Immuno-Trol" and "NWB was also tested under the same conditions." (Specific number of samples and country of origin are not explicitly provided. Implies prospective testing.)
Assay Precision: "Immuno-Trol on different instrument-operator combinations and over multiple test days using one-color and four-color and four-color monoclonal antibody reagents. NWB and CYTO-TROL were also tested under the same conditions." (Specific number of samples, test days, country of origin, and whether retrospective/prospective are not explicitly provided. Implies prospective testing.)

Overall Data Provenance: The company, Coulter Corporation, is based in Miami, Florida, USA. Therefore, it is highly likely the data provenance is USA. The studies are described as "Product testing to assess the performance," implying they are prospective studies conducted by the manufacturer for regulatory submission.

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

The concept of "ground truth" as typically applied to AI/diagnostic imaging (e.g., expert consensus) is not applicable here. This document describes the performance of a quality control material intended to verify the performance of other diagnostic reagents and methods, not to provide a diagnosis itself. The "ground truth" for this device is its inherent, manufactured cellular composition and expected reactivity with specific antibody reagents, which are compared against established performance specifications.

4. Adjudication Method for the Test Set

Not applicable. As this is a performance study for a quality control material, not a clinical diagnostic device requiring expert interpretation of results, there is no adjudication method in the traditional sense (e.g., 2+1, 3+1). The "ground truth" is defined by the product's design and manufacturing specifications.

5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study

No, a MRMC comparative effectiveness study was not done. This type of study is typically performed for diagnostic imaging devices or algorithms where human readers interpret cases. The IMMUNO-TROL device is a quality control material.

6. Standalone (Algorithm Only) Performance Study

No, a standalone (algorithm only) performance study was not done. The IMMUNO-TROL is a physical control cell product, not an algorithm. Its performance is intrinsically linked to its use with flow cytometry instruments and monoclonal antibody reagents.

7. Type of Ground Truth Used

The "ground truth" for the performance evaluation of IMMUNO-TROL is based on established manufacturing specifications and expected reactivity of the control cells with monoclonal antibody reagents for immunophenotyping. This constitutes an analytical truth rather than a clinical ground truth like pathology or outcome data. The "Acceptance Criteria" mentioned throughout the document are derived from these internal specifications. The predicate devices (NWB and CYTO-TROL) also served as a comparative benchmark to ensure comparable performance.

8. Sample Size for the Training Set

Not applicable. The IMMUNO-TROL is not an artificial intelligence or machine learning device that requires a "training set." It is a manufactured quality control product.

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

Not applicable. As there is no training set for this product.

Summary

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COULTER CORPORATIONPO. BOX 169015Miami, Florida 33116-9015 USA	Date: January 22, 1999
Customer Service: (800) 526-7694	Title: Summary of Safety and Effectiveness Information For 510(k) Premarket Notification
Product Information: (800) 526-6932(800) 327-6531 (305) 327-6531	Product: IMMUNO-TROL TM Control Cells
www.coulter.com
Company:	Coulter Corporation11800 SW 147 AvenueMiami, FL 33196-2500
Contact:	Dr. Marion S. Gaide (M/C: 31-B06)Senior Regulatory Affairs SpecialistPremarket Regulatory Affairs(305) 380-2594
Telephone:	(305) 380-2594
Common or Usual or Classification Name:	Whole Blood Control for Imunophenotyping
Product Classification:	Product Code: 81 JPK; C.F.R. Section: 864.8625; ClassificationPanel: Hematology and Pathology Devices; Device Class: II
Intended Use:	IMMUNO-TROL TM Control Cells (Immuno-Trol) is an assayed, lysable whole blood quality controlproduct for immunophenotyping analysis using monoclonal antibody reagents and flow cytometry. Itprovides a positive cell control that is processed in the same manner as a whole blood sample. Thisallows verification of reagent performance, and the methods used for staining of targeted cells, lysingerythrocytes, and analyzing samples by flow cytometry. CD populations intended "For In VitroDiagnostic Use" and those intended "For Research Use Only. Not For Use In Diagnostic Procedures."are given in separate tables in the TABLE OF EXPECTED RESULTS section of the Immuno-Trolpackage insert.
	Substantial Equivalence: 510(k) Premarket Notification: K894651
	COULTER TM CYTO-TROL TM Control Cells Kit (CYTO-TROL)
Product Comparison:	Immuno-Trol is essentially identical to the combined capabilities and intended uses of the two PredicateSystem components, Normal Whole Blood (NWB) and CYTO-TROL. It also achieves the samepurpose as two other Hematology Quality Control Materials for immunophenotyping by flowcytometry currently distributed "For In Vitro Diagnostic Use." Similar to CYTO-TROL, Immuno-Trolprovides an assayed positive cell control material consisting of leukocytes with surface antigensdetectable by monoclonal antibodies using, for example, CYTO-STAT ® , CYTO-STAT ® /COULTERCLONE ® and IOTest ® Reagents. However, Immuno-Trol expands the capabilities of CYTO-TROL byfeaturing more surface antigens. The NWB component of the Predicate System also consists ofleukocytes with surface antigens detectable by monoclonal antibodies and may be used in lieu of anassayed cell control product. However, NWB is unassayed material and the specific surface antigenspresent in a sample are unknown prior to immunophenotyping analysis using one or more monoclonalantibody reagents and flow cytometry. Further, when using NWB to QC immunophenotypingparameters and procedures, the percent positive and absolute count results obtained for targeted cellularpopulations must be compared to results representative of the Site's normal human donor pool. Similarto NWB, the erythrocyte component of Immuno-Trol can be lysed using a whole blood lysing methodsuch as COULTER ® ImmunoPrep TM Reagent System and Workstation (ImmunoPrep). NWB andCYTO-TROL are the same in that the Standard (Indirect) Method which combines hematology andflow

surface antigens detected are defined by the reagent(s) being assessed for monoclonal antibody activity. Science Serving Humanity

flow cytometry results can be used to calculate absolute count results. Immuno-Trol and NWB are the same in that both can be used with the absolute count reagent, COULTER® Flow-Count™ Fluorospheres (Flow-Count) for the direct determination of absolute count by flow cytometry. Finally, Immuno-Trol, NWB and CYTO-TROL are the same in that the gating population, gating method and .

4232216-F R 6-97

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Product testing to assess the performance of Immuno-Trol is described below. Studies were designed Product Testing: in line with instructions for use in the product package insert and performance specifications. NWB and CYTO-TROL samples were also assayed for comparison purposes. The results of product testing demonstrated that Immuno-Trol meets all performance specifications and provides Percent Positive (%) and Absolute Count Results comparable to those of NWB and CYTO-TROL and also within the Acceptance Criteria for each leukocyte surface antigen given in the Immuno-Trol package insert.

Vial-to-Vial Reproducibility:

Reproducibility (that is, Homogeneity) was assessed by measuring the Red Blood Cell (RBC) and White Blood Cell (WBC) concentrations of filled vials of Immuno-Trol on the COULTER® STKS™ Analyzer (STKS). The filled vials were sampled from Immuno-Trol lots at regular intervals across the fill. The study results were expressed in terms of cells/mL and all values met the Acceptance Criteria. These data demonstrate the consistency and reproducibility of Immuno-Trol filled vials.

2. Lot-to-Lot Reproducibility:

Reproducibility was assessed by testing Immuno-Trol on different instrument-operator combinations using one-color, two-color three-color and four-color monoclonal antibody reagents. Testing produced overall percent positive (%) and absolute count (as applicable) results for the leukocyte surface antigens given in the Immuno-Trol Package Insert. The study results were expressed in terms of percent positive (%) and absolute count (cells/uL) and all values met the Acceptance Criteria. These data demonstrate the consistency and reproducibility of Immuno-Trol between lots.

3. Stability Studies:

Closed Vial, Open Vial and Stored Prepared Sample stability characteristics and claims for Immuno-Trol were assessed with two study protocols: "Closed Vial: 90 days at 2-8℃; Open Vial: 30 days at 2-8℃" and "Stored Prepared Sample: 2 hours at 20-25°C; 24 hours at 2-8°C." Immuno-Trol was tested using one-color, threecolor and four-color monoclonal antibody reagents under the different storage and temperature conditions over test periods extending up to and beyond the respective 90-day and 30-day dains. The study results were expressed in terms of percent positive (%) and absolute count (cells/uL) and all values met the Acceptance Criteria. These data demonstrate Immuno-Trol meets both reagent and sample stability characteristics and claims under the storage and temperature conditions studied.

1. Absolute Count Method Verification:
  Absolute count method was assessed by testing Immuno-Trol using three-color and four-color monoclonal antibody reagents and the Flow-Count (Direct) Method and the Standard (Indirect) Method for absolute count determination. NWB was also tested under the same conditions. The study results were expressed in terms of percent positive (%) and absolute count (cells/uL) and all values met the Acceptance Criteria. In addition, both the Flow-Count (Direct) Method and the Standard (Indirect) Method provided essentially identical absolute count results for Immuno-Trol and NWB. These data clearly demonstrate the suitability of using the Flow-Count (Direct) Method for absolute count determination of Immuno-Trol leukocyte surface antigens.
1. Assay Precision:
  Assay precision (that is, reproducibility) was assessed by testing Immuno-Trol on different instrument-operator combinations and over multiple test days using one-color and four-color and four-color monoclonal antibody reagents. NWB and CYTO-TROL were also tested under the same conditions. The study results were expressed in terms of percent positive (%) and absolute count (cells/uL) and analyzed in terms individual and combined assay precision for the various study parameters. All values met the Acceptance Criteria. In addition, Immuno-Trol, NWB and CYTO-TROL varied little as evidenced by the means, standard deviations and coefficients of variation for the different sets of measurements. These data demonstrate Immuno-Trol performs in a manner comparable to the Predicate System components, NWB and CYTO-TROL.

Marion S. Gaide, Ph.D.

Senior Regulatory Affairs Specialist Corporate Regulatory Affairs

January 22, 1999
Date

trolse

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DEPARTMENT OF HEALTH & HUMAN SERVICES

Image /page/2/Picture/2 description: The image shows the seal of the Department of Health & Human Services - USA. The seal is circular and contains the words "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" around the perimeter. In the center of the seal is an abstract image of an eagle.

MAR 1 6 1999

Marion S. Gaide, Ph.D. Senior Regulatory Affairs Specialist Premarket Regulatory Affairs Coulter Corporation 11800 SW 147 Avenue Miami, Florida 33196-2500

Re: K984216 Trade Name: IMMUNO-TROL™ Control Cells Regulatory Class: II Product Code: JPK Dated: February 22, 1999 Received: February 23, 1999

Dear Dr. Gaide:

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.

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

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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 Sutman

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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Page 1 of 1

INDICATIONS FOR USE

510(k) Number (if known): K984216

IMMUNO-TROL™ Control Cells Device Name:

Indications For Use:

Steve G. Maher

(Division Sign-Om
Division of Clinical Laboratory Devices
510(k) Number L984216

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

Concurrence of CDRH, Office of Device Evaluation (ODE)

V Prescription Use (Per 21 CFR 801.109)

Over-The-Counter Use

510i4us2

Regulation Number and Section

§ 864.8625 Hematology quality control mixture.

(a)
Identification. A hematology quality control mixture is a device used to ascertain the accuracy and precision of manual, semiautomated, and automated determinations of cell parameters such as white cell count (WBC), red cell count (RBC), platelet count (PLT), hemoglobin, hematocrit (HCT), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), and mean corpuscular hemoglobin concentration (MCHC).(b)
Classification. Class II (special controls). Except when intended for use in blood components, the device is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 864.9.