CYTO-STAT TRICHROME CD8-FITC/CD4-RDI/CD3-PC5 MONOCLONAL ANTIBODY REAGENT WITH CYTO-STAT TRICHROME MSIGGI-FITC/MSIGGI-RD1
Applicant
Coulter Corp.
Product Code
GKZ · Hematology
Decision Date
Dec 23, 1996
Decision
SESE
Submission Type
Traditional
Regulation
21 CFR 864.5220
Device Class
Class 2
Indications for Use
CYTO-STAT® triCHROME™ CD8-FITC/CD4-RD1/CD3-PC5 Monoclonal Antibody Reagent is a three-color fluorescent reagent comprised of three murine monoclonal antibodies. Each antibody is labeled with a different color fluorochrome. The reagent allows simultaneous identification and enumeration of total CD3+, total CD4+, total CD8+, dual CD3+/CD4+ and dual CD3+/CD8+ lymphocytes in whole blood by flow cytometry. An isotypic control, CYTO-STAT® triCHROME™ MsIgG1-FITC/MsIgG1-RD1/MsIgG1-PC5, is used to monitor nonspecific staining. CYTO-STAT® triCHROME™ MsIgG1-FITC/MsIgG1-RD1/MsIgG1-PC5 Isotypic Control is a three-color fluorescent reagent comprised of three murine monoclonal antibodies. Each antibody is labeled with a different color fluorochrome. This product is intended for use as a quality control reagent to monitor the levels of nonspecific antibody binding in cell surface staining procedures which use CYTO-STAT® triCHROME™ CD8-FITC/CD4-RD1/CD3-PC5 Monoclonal Antibody Reagent to identify and enumerate total CD3+, total CD4+, total CD8+, dual CD3+/CD4+ and dual CD3+/CD8+ lymphocytes in whole blood by flow cytometry.
Device Story
Device consists of three-color fluorescent murine monoclonal antibody reagents (CD8-FITC/CD4-RD1/CD3-PC5) and corresponding isotypic controls. Used in clinical laboratories by trained personnel to perform immunophenotyping of whole blood via flow cytometry. Reagents bind to specific lymphocyte surface markers; fluorochromes allow simultaneous detection of multiple cell populations (CD3+, CD4+, CD8+). Flow cytometer (e.g., COULTER® EPICS® XL-MCL) measures immunofluorescence; software gates on lymphocytes to identify and enumerate cell subsets. Output provides percentage and absolute counts of T-lymphocyte populations. Results assist clinicians in assessing immune status in patients with conditions like HIV, autoimmune disease, or post-transplant status.
Clinical Evidence
Bench testing and comparative clinical study. Accuracy evaluated using normal and abnormal (HIV, transplant, autoimmune) blood specimens (n=diverse population, ages 18-85). Specimens assayed in parallel with predicate device. Metrics included regression/correlation analysis, means, SD, and 95% CIs. Results showed identical enumeration of targeted lymphocytes. Linearity confirmed via serial dilution of control cells. Precision (within-run and interlaboratory) demonstrated via CV analysis. No clinical diagnostic outcomes reported; study focused on analytical performance equivalence.
Technological Characteristics
Three-color fluorescent murine monoclonal antibody reagent. Fluorochromes: FITC, RD1, PC5. Principle: Immunofluorescence analysis via flow cytometry. Connectivity: Standalone reagent system for use with flow cytometers (e.g., COULTER® EPICS® XL-MCL). Sterilization: Not specified. Software: Rule-based gating for lymphocyte identification.
Indications for Use
Indicated for the identification and enumeration of total CD3+, total CD4+, total CD8+, dual CD3+/CD4+, and dual CD3+/CD8+ lymphocytes in whole blood samples from patients (ages 18-85, including those with HIV, organ transplants, or autoimmune disease) using flow cytometry.
Regulatory Classification
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.
Special Controls
*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.”
Predicate Devices
CYTO-STAT®/COULTER CLONE® CD3-ECD/T4-RD1/T8-FITC Monoclonal Antibody Reagent with CYTO-STAT®/COULTER CLONE® MsIgG2b-ECD/MsIgG1-RD1/MsIgG1-FITC Isotypic Control (K950742)
Submission Summary (Full Text)
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DEC 23 1996
K964618
COULTER
COULTER CORPORATION
P.O. BOX 169015
Miami, Florida 33116-9015 USA
Customer Service: (800) 526-7694
Product Information: (800) 526-6932
(305) 380-3800
(800) 327-6531
Date: October 11, 1996
Title: Summary of Safety and Effectiveness Information for "K950742 510(k) Additional Information"
Coultor Corporation
Miami, Florida USA
Coultor Leasing Corporation
Miami, Florida USA
Coultor Electronics, Pty. Ltd.
Sydney, Australia
Coultor Electronics Ind. & Com., Ltda.
Rio de Janeiro, Brazil
Coultor Electronics of Canada, Ltd.
Burlington, Ontario, Canada
Coultor Electronics, Ltd.
Luton Bedfordshire, England
Coultor Electronics France, S.A.
Margency, France
Coultor Electronics GmbH
Krefeld, Germany
Coultor Electronics (HK), Ltd.
Hong Kong
Coultor K. K.
Tokyo, Japan
Coultor de Mexico S.A., DE C.V.
Mexico City, Mexico
Coultor Electronics, Ltd.
Mijdrecht, Netherlands
Coultor Electronics, Pty. Ltd.
Auckland, New Zealand
Coultor Electronics Sales of P.R., Inc.
San Juan, Puerto Rico
Coultor Electronics, Ltd.
Johannesburg, South Africa
Coultor Electronics, Ltd.
Istanbul, Turkey
Coultor Electronics, S.A.
Caracas, Venezuela
Product: CYTO-STAT® triCHROME™ CD8-FITC/CD4-RD1/CD3-PC5 Monoclonal Antibody Reagent with CYTO-STAT® triCHROME™ MsIgG1-FITC/MsIgG1-RD1/MsIgG1-PC5 Isotypic Control
Company: Coulter Corporation
11800 SW 147 Avenue
Miami, FL 33196-2500
Contact: Dr. Marion S. Gaide (M/C: 31-B06)
Senior Regulatory Affairs Specialist
Corporate Regulatory Affairs
Telephone: 305-380-2594
Common or Usual or Classification Name: Lymphocyte Immunophenotyping Monoclonal Antibody Reagent and Isotypic Control
Product Classification: Product Code: GKZ; C.F.R. Section: 864.5220
Classification Panel: Hematology and Pathology Devices; Device Class: II
Intended Use: CYTO-STAT® triCHROME™ CD8-FITC/CD4-RD1/CD3-PC5 Monoclonal Antibody Reagent is a three-color fluorescent reagent comprised of three murine monoclonal antibodies. Each antibody is labeled with a different color fluorochrome. The reagent allows simultaneous identification and enumeration of total CD3+, total CD4+, total CD8+, dual CD3+/CD4+ and dual CD3+/CD8+ lymphocytes in whole blood by flow cytometry. An isotypic control, CYTO-STAT® triCHROME™ MsIgG1-FITC/MsIgG1-RD1/MsIgG1-PC5, is used to monitor nonspecific staining.
CYTO-STAT® triCHROME™ MsIgG1-FITC/MsIgG1-RD1/MsIgG1-PC5 Isotypic Control is a three-color fluorescent reagent comprised of three murine monoclonal antibodies. Each antibody is labeled with a different color fluorochrome. This product is intended for use as a quality control reagent to monitor the levels of nonspecific antibody binding in cell surface staining procedures which use CYTO-STAT® triCHROME™ CD8-FITC/CD4-RD1/CD3-PC5 Monoclonal Antibody Reagent to identify and enumerate total CD3+, total CD4+, total CD8+, dual CD3+/CD4+ and dual CD3+/CD8+ lymphocytes in whole blood by flow cytometry.
Substantial Equivalence: "K950742 510(k) Premarket Notification"
CYTO-STAT®/COULTER CLONE® CD3-ECD/T4-RD1/T8-FITC Monoclonal Antibody Reagent with
CYTO-STAT®/COULTER CLONE® MsIgG2b-ECD/MsIgG1-RD1/MsIgG1-FITC Isotypic Control
Science Serving Humanity
4232216-E R 11-94
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# Product Differences:
CD8/CD4/CD3 with MsIgG1/MsIgG1/MsIgG1 and CD3/T4/T8 with MsIgG2b/MsIgG1/MsIgG1 are essentially identical with respect to features and principles of operation. Both the revised and original product systems use the same, well-established, state-of-the-art technologies of immunophenotyping with monoclonal antibodies and flow cytometry to measure cellular components in whole blood via immunofluorescence analysis. Further, the intended use of each system is the same. The liquid monoclonal antibody reagents allow simultaneous identification and enumeration of more than one lymphocyte population (total CD3+, total CD4+, total CD8+, dual CD3+/CD4+ and dual CD3+/CD8+) in a single specimen using a single reagent. Each system also uses separate reagents to 1) identify a lymphocyte gate (i.e., CYTO-STAT®/COULTER CLONE® Mo2-RD1/KC56 (T-200)-FITC); and 2) monitor nonspecific binding (i.e., isotypic control).
The few differences (italicized) between the reagent and isotypic control formulations are as follows:
1. CD3 Clone: CD8/CD4/CD3: UCHT1
CD3/T4/T8: HIT3a
2. CD3 Isotype: CD8/CD4/CD3: MsIgG1
CD3/T4/T8: MsIgG2a
3. Isotypic Control Clone: MsIgG1/MsIgG1/MsIgG1: ————; MsIgG1=2T8-2F5
MsIgG2b/MsIgG1/MsIgG1: MsIgG2b=MPC11; MsIgG1=2T8-2F5
4. Isotypic Control Isotype: MsIgG1/MsIgG1/MsIgG1: ————; MsIgG1
MsIgG2b/MsIgG1/MsIgG1: MsIgGb; MsIgG1
5. CD3 Fluorochrome: CD8/CD4/CD3: PC5 (Phycoerythrin-Cy5)
CD3/T4/T8: ECD (Energy-Coupled Dye)
# Product Testing:
Product testing to assess the performance of the CD8/CD4/CD3 product system is described below. Studies were designed in line with instructions for use given in the Package Inserts, Product Manuals, and performance specifications. Specimens were assayed with the CD3/T4/T8 product system for comparison purposes. The results of product testing demonstrated that CD8/CD4/CD3 met all performance specifications and provided mature T (CD3+), inducer T (CD4+; dual CD3+/CD4+) and suppressor/cytotoxic T (CD8+; dual CD3+/CD8+) T lymphocyte values comparable to those of CD3/T4/T8.
## 1. Accuracy:
Normal and abnormal (e.g., Human Immunodeficiency Virus, organ transplant, autoimmune disease, low white blood cell count) whole blood specimens were collected from geographically diverse populations of males and females unselected as to race and ranging in age from 18 to 85 years. Specimens were divided, processed as lysed preparations and assayed in parallel with CD8/CD4/CD3 and CD3/T4/T8. The CD3+, CD4+, CD8+, CD3+/CD4+ and CD3+/CD8+ percentages expressed in terms of the total lymphocyte count and absolute counts (cells/μL) were determined with a COULTER® EPICS® XL-MCL flow cytometer gated on lymphocytes. White blood cell counts and 5-part differentials were obtained for all specimens using the COULTER® STKS. Absolute counts were determined using both the Standard (Indirect) Method, and the Flow-Count (Direct) Method with Flow-Count™ Fluorospheres. All 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, confidence intervals with 95% limits, regression and correlation analyses, and analyses of variance demonstrated that CD8/CD4/CD3 and CD3/T4/T8 identify and enumerate essentially identical numbers of the targeted lymphocytes in whole blood specimens.
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2. Linearity:
Three replicate measurements were made on a concentrated COULTER™ CYTO-TROL™ Control Cells sample serially diluted to achieve a range of CD3+, CD4+ (CD3+/CD4+) and CD8+ (CD3+/CD8+) lymphocyte concentrations. Samples were assayed with CD8/CD4/CD3 and analyzed on a COULTER® EPICS® XL-MCL flow cytometer gated on lymphocytes. Values were expressed in terms of absolute counts (cells/μL).
Results analyzed in terms of regression and correlation analyses for recovered versus expected absolute counts demonstrated linearity of the assay.
3. Within Run (Intralaboratory) Precision:
Ten replicate measurements were made for each of three levels of CD3+, CD4+ (CD3+/CD4+) and CD8+ (CD3+/CD8+) lymphocyte concentrations using a COULTER® EPICS® XL-MCL flow cytometer gated on lymphocytes. Levels were obtained by selective depletions of a normal whole blood specimen and assayed with CD8/CD4/CD3. Values were expressed in terms of % of the total lymphocyte count.
Results analyzed in terms of mean ± 1 SD and CV demonstrated Within Run (Intralaboratory) Precision of the assay.
4. Interlaboratory Precision:
Ten replicate measurements were made on the same day using different laboratories and COULTER® EPICS® XL-MCL flow cytometers. All measurements were made on a single normal whole blood specimen divided and assayed with CD8/CD4/CD3. Values were expressed in terms of % of the total lymphocyte count.
Results analyzed in terms of mean ± 1 SD and CV demonstrated Interlaboratory Precision of the assay.
Marion S. Gaide, Ph.D.
Senior Regulatory Affairs Specialist
Corporate Regulatory Affairs
October 11, 1996
Date
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