For the FACS® family of flow cytometers equipped with a blue (488-nm) and a red t diode (635-nm) laser.
A monoclonal antibody reagent for identification and enumeration of mature human T . lymphocyte subsers in human peripheral blood.
For use with crythrocyte lysed whole blood. .
To characterize and monitor forms of autoimmune diseases, such as lupus. .
To characterize and monitof congenital or acquired immunodeficiencies, such as . SCID or AIDS.
For in vitro diagnostic use.

Device Description

The Becton Dickinson CD3 fluorescein isothiocyanate (FITC)/CD8 phycoerythrin (PE)/CD45 peridinin chlorophyll protein (PerCP)/CD4 allophycocyanin (APC) reagent is a four-color, direct immunofluorescence reagent for identifying and enumerating percentages of CD3+ T Lymphocytes, CD3+CD4+ helper/inducer, and CD3+CD8+ suppresser/cyroroxic T-Lymphocyte subscts in erythrocyce-lysed whole blood. Each vial of reagent yields 50 tests. The reagent is intended for use on the Becton Dickinson FACSCalibur 10 flow cycomerers equipped with the FL4 Option, the Apple Macintosh Quadra or PowerPC computer, and CELLQuest or MultiSET software. Daily instrument set-up requires CaliBRITE beads (unlabeled, FITC, PE, Per CP, and APC) and FACSComp software.

AI/ML Overview

Here's an analysis of the provided text to extract the acceptance criteria and supporting study details:

Note: The provided document is a 510(k) summary for a medical device (MultiTEST CD3/CD8/CD45/CD4 reagent). These summaries often focus on demonstrating substantial equivalence to a predicate device rather than explicitly stating pre-defined "acceptance criteria" and then proving each one. Instead, they describe performance testing to show the new device is "as safe and effective" as the predicate. Therefore, the "acceptance criteria" in this context are interpreted from the performance claims and the comparison to an equivalent device. The "reported device performance" is the general finding of "acceptable" or "equivalent" performance in each study.

Acceptance Criteria and Study Details for MultiTEST CD3/CD8/CD45/CD4 Reagent

1. Table of Acceptance Criteria and Reported Device Performance

Acceptance Criteria (Inferred)	Reported Device Performance
Accuracy: Equivalence to predicate three-color reagents (TriTEST CD3/CD8/CD45 and TriTEST CD3/CD4/CD45).	Demonstrated equivalence to predicate devices (MultiTEST CD3/CD45/CD4 is equivalent to TriTEST CD3/CD8/CD45 and TriTEST CD3/CD4/CD45).
Within-site Reproducibility: Acceptable variability in T-cell count measurements at a single site.	Demonstrated acceptable within-site reproducibility.
Across-site Reproducibility: Acceptable variability in T-cell count measurements across multiple sites.	Demonstrated acceptable across-site reproducibility.
Stability (Whole Blood Storage): Acceptable performance for samples stored up to 48 hours after blood draw.	Demonstrated acceptable stability of samples prepared up to 48 hours after blood draw.
Stability (Stained Sample Storage): Acceptable performance for stained samples acquired up to 24 hours after preparation.	Demonstrated acceptable stability of prepared samples up to 24 hours after preparation.
Linearity and Recovery: Linear response and acceptable recovery over a specified range of WBC and lymphocyte counts.	Indicated linear response over the range of 200-29,700 WBC/uL and 100-9000 Lymphocytes/uL, with acceptable recovery.
Overall Equivalence: As safe and effective as the predicate devices, sharing the same intended uses and methodologies.	The device is as safe and effective as the predicate device; products yield essentially equivalent performance characteristics.

2. Sample Size and Data Provenance for Test Set

Accuracy Study: 129 specimens (70 normal, 59 abnormal).
Within-site Reproducibility Study: 9 donors (3 normal, 6 abnormal), with each specimen divided into 10 aliquots (total 90 samples tested).
Across-site Reproducibility Study: 46 donors (15 normal, 31 abnormal), with each specimen divided into 5 aliquots (total 230 samples tested).
Stability Studies: 30 donors (10 normal, 20 abnormal).
Linearity and Recovery Study: 3 normal donors.

Data Provenance: The studies were performed at:

Children's Memorial Hospital, Chicago, Illinois (USA)
Covance Central Laboratory, Indiana (USA)
Cleveland Clinic Foundation, Cleveland, Ohio (USA)
Becton Dickinson Immunocytometry Systems, San Jose, California (USA)

The data appears to be prospective for the purpose of demonstrating device performance, as these were specific studies designed for the 510(k) submission.

3. Number of Experts and Qualifications for Ground Truth (Test Set)

The document does not explicitly state the number of experts or their qualifications for establishing ground truth for the test set in the conventional sense of human readers for an image. For flow cytometry, "ground truth" is typically established by the reference method (e.g., the predicate device or a clinical laboratory's established procedures for manual cell counting/analysis) and the technical accuracy of the instrument. The "performance data" section describes the studies comparing the new device against the predicate or expected biological ranges.

4. Adjudication Method (Test Set)

Not applicable. This is not a study requiring adjudication by human readers for diagnostic interpretation. The "adjudication" is internal to the flow cytometer's software (MultiSET software's single-tube fluorescence gating and automated quality control algorithms) and comparison to predicate device results.

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

No, a Multi-Reader Multi-Case (MRMC) comparative effectiveness study was not done. This type of study is typically performed for imaging diagnostics where human readers interpret images with and without AI assistance. This device is a diagnostic reagent for flow cytometry, which involves automated enumeration of cell populations rather than human interpretation of complex images.

6. Standalone Performance Study

Yes, a standalone performance was done for various aspects of the device's function:

Accuracy: Comparing the new 4-color reagent to the predicate 3-color reagents using the same specimen.
Reproducibility (within-site and across-site): Assessing the consistency of results generated by the device.
Stability: Evaluating the device's performance under different storage conditions.
Linearity and Recovery: Determining the device's ability to accurately measure cell concentrations across a range.

These studies assess the device's performance in isolation with human involvement mainly in sample preparation and operation.

7. Type of Ground Truth Used

The primary ground truth used for the performance studies was comparison to a legally marketed predicate device. Specifically:

For accuracy, the results from the new device (MultiTEST CD3/CD45/CD4) were compared to those obtained using the predicate devices (TriTEST CD3/CD8/CD45 and TriTEST CD3/CD4/CD45).
For other performance metrics (reproducibility, stability, linearity), the ground truth was implied by the expected biological ranges for "normal" and "abnormal" donors and the device's ability to consistently and accurately measure these populations against established laboratory methods.

8. Sample Size for the Training Set

The document does not provide information on a specific "training set" for an algorithm in the way that an AI deep learning model would have. The "MultiSET software" includes automated quality control algorithms, but no details are given about a distinct training set for these algorithms. The development of such software would have involved internal validation and calibration using various samples, but this information is not disclosed in the 510(k) summary.

9. How Ground Truth for the Training Set Was Established

As no specific training set is outlined in the document, how ground truth for such a set was established is not provided. If the "MultiSET software" involved machine learning or complex algorithms, its development would have required internal validation and calibration, likely using well-characterized samples or a gold standard method. However, this is outside the scope of the information provided in the 510(k) summary.

Summary

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MAR 1 1 1998

510(k) Summary

This summary of 510(k) safety and effectiveness information is being submitted in accordance with the requirements of SMDA 1990 and 21CFR807.92.

The assigned 510(k) number is K974360.

Submitter Information (21 CFR 807.92(a)(1))

Submirrer: Becton Dickinson Immunocyrometry Systems 2350 Qume Drive San Jose, CA 95131-1807

Contact: Cindy Morrow Sr. Regulatory Specialist (408) 954-2694

November 18, 1997 Summary date:

Name of Device and Classification (21 CFR 807.92(a)(2))

MultiTEST CD3/CD8/CD45/CD4 Name:

Classification: Class II Device

Predicate Device (21 CFR 807.92(a)(3))

MultiTEST CD3/CD8/CD45/CD4 reagent and TRUCOUNT absolute count tubes are substantially equivalent" to TriTEST CD3/CD8/CD45 (K970326), TriTEST CD3/CD4/CD45 (K965053), TRUCOUNT tubes (K970836) and MultiSET software (K963963).

Description of the Device (21 CFR 807.92(a)(4))

" The term "substantial equivalence" as used in this 510(k) notification is limited to the definition of substantial equivalence as found in the Federal Food, Drug, and Cosmetic Acr, as annended and as applied under 21 CFR 807, Subpart B under which a device can be marketed withour pre-marker approval or reclassification of substantial equivalency under this notification is not inrended to have any bearing whassever on the resolution of parent infringement suits or any other patent marrers. No statements related to, or in support of substantial equivalence herein shall be construed as an admission against interest under the US Parent Laws or their application by the courts.

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The four-color method permits the identification and enumeration of helper/inducer and suppresser/cytotoxic T-Lymphocyte subsets using MultiSET software's single-tube fluorescence gating and automated quality control algorithms. A lymphocyce gate is drawn for the CD45* leucocytes with low side scarter and the T-Lymphocyce subsers are provided as an absolute count or percentage of total lymphocytes.

Intended Use (21 CPR 807.92(a)(5))

MultiTEST CD3/CD8/CD45/CD4 reagent is a four-color reagent for identifying and enumerating CD3+ T Lymphocytes, CD3+CD4* helper/inducer, and CD3+CD8+ suppresser/cytoroxic T-Lymphocyte subsets by direct immunofluorescence. Subsets of T Lymphocytes are useful in managing immunodeficiency diseases. To characterize and monitor congenital or acquired immunodeficiencies, such as SCID or AIDS.

Technological Characteristics (21 CFR 807.92(a)(6))

MultiTEST CD3/CD8/CD45/CD4 is a four-color reagent and TriTEST CD3/CD8/CD45 and TriTEST CD3/CD4/CD45 are three-color reagents. The three and four-color reagents all employ the same monoclonal antibody clones, however the CD4 antibody is conjugated to PE in the three-color reagent and to APC in the four-color reagent. The three-color reagent includes FITC, PE, and PerCP fluorescent dyes that are excited by the flow cytometer's blue (488-nm) argon-ion laser. The four-color reagent contains an additional APC fluorescent dyc. The APC is excited by a red diode (635-am) laser provided in Bector Dickinson's FL4 Option for the FACSort and FACSCalibur flow cytometers.

Performance Data (21 CFR 807.92(b)(2))

Performance of the product was established by testing at Children's Memorial Hospiral, Chicago, Illinois; Covance Central Laboratory, Indiana; Cleveland Clinic Foundation Cleveland, Ohio; of Becton Dickinson Immunocycomerry Systems, San Jose, California.

Several studies were performed:

· Accuracy was determined by comparing results from lysed whole blood (LWB) specimens stained with both the three- and four-color reagents on the FACSCalibur. A total of 129 specimens, including 70 normals and 59 abnormals were obtained and analyzed at two clinical sites. Accuracy data demonstrated that MultiTEST CD3/CD45/CD4 is equivalent to TriTEST CD3/CD8/CD45 and TriTEST CD3/CD4/CD45.
· Within-site reproducibility was performed on LWB specimens from 3 normal and 6 abnormal donors across the range of low (100-350), medium (350-700), and high (5700) CD4+ T cell counts (cells/L). Each specimen was divided into 10 aliquots and then stained and analyzed using a FACSCalibur system. Results demonstrated acceptable within-site reproducibility.

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@ 005
· Across-site reproducibility was performed at three clinical sites on LWB specimens from a total of 15 normal and 31 abnormal donors across the same range of low, medium, and high CD4+ T cell counts (cells/uL). Each specimen was divided into 5 aliquots and then stained and analyzed using a FACSCalibur system. Results demonstrated acceptable across site reproducibility.
· Stability studies were conducted at one site using samples from 10 normal and 20 abnormal donors. The studies assessed changes associated with the storage of whole blood prior to staining, changes as a result of time between staining and dara acquisition, and the combined effect of time of storage and time after staining. Results demonstrate acceptable stability of samples prepared up to 48 hours after blood draw and stability of prepared samples up to 24 hours after preparation.
Lincarity and recovery was determined using blood specimens from 3 normal donors diluted to 5 different concentrations, ranging from 200 to 29,700 WBC/uL and from 100 to 9000 Lymphocytes/uL. Results indicate linear response over this range and acceptable recovery.

Comparison to Predicate Device (21 CFR 807.92(b)(3))

The results of the clinical studies demonstrate that the device is as safe and effective as the predicate device. The four-color MultiTEST CD3/CD8/CD45/CD4 reagent is substantially equivalent to the predicate three-color TriTEST CD3/CD4/CD45 and TriTEST CD3/CD8/CD45 reagents, in that they share the same inrended uses and methodologies. Results demonstrate that the products yield essentially equivalent performance characteristics.

Cindy Monroe

Cindy Morrow Sr Regulatory Specialist

3/4/98

Date

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Image /page/3/Picture/1 description: The image shows the seal of the Department of Health & Human Services-USA. The seal is circular, with the words "DEPARTMENT OF HEALTH & HUMAN SERVICES-USA" arranged around the top half of the circle. In the center of the seal is a stylized image of an eagle with its wings spread, with three wavy lines below the eagle. The eagle and wavy lines are black, and the background is white.

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

Ms. Cindy Morrow Sr. Regulatory Specialist Becton Dickinson Immunocytometry Systems 2350 Qume Drive San Jose, CA 95131-1807

MAR 1 1 1998

Re: K974360 Trade Name: Multitest CD3/CD8/CD45/CD4 Regulatory Class: II Product Code: GKZ Dated: December 17, 1997 Received: December 18, 1997

Dear Ms. Morrow:

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 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 at (301) 443-6597 or at its internet address "http://www.fda.gov/cdrh/dsmamain.html"

Sincerely yours.

Steven Autman

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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Attachment A Indications for Use Statement

Device Name:

MultiTEST CD3/CD8/CD45/CD4

Indications For Use:

For the FACS® family of flow cytometers equipped with a blue (488-nm) and a red t diode (635-nm) laser.
A monoclonal antibody reagent for identification and enumeration of mature human T . lymphocyte subsers in human peripheral blood.
For use with crythrocyte lysed whole blood. .
To characterize and monitor forms of autoimmune diseases, such as lupus. .
To characterize and monitof congenital or acquired immunodeficiencies, such as . SCID or AIDS.
For in vitro diagnostic use.

Peter E. Mckin
(Division Sign-Off)

(Division Sign-Off)
Division of Clinical Laboratory Devices

510(k) Number _

Prescription Use V (Per 21 CFR 801.109)

Over-The Counter Use

(Optional Format 1-2-96)

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.”