BD Multitest™ 6-color TBNK reagent with optional BD Trucount™ tubes is a sixcolor direct immunofluorescence reagent for use with BD FACSCanto™ and BD FACSCanto™ II flow cytometers to identify and determine the percentages and absolute counts of T, B, and natural killer (NK) cells as well as the CD4 and CD8 subpopulations of T cells in peripheral blood.

BD Multitest 6-color TBNK reagent and BD Trucount tubes can be used with the BD FACS™ Loader.

Device Description

Human lymphocytes can be divided into three major subset populations based on their biologic function and cell-surface antigen expression: T Ivmphocytes (CD3+), B lymphocytes (CD19+), and Natural Killer (NK) cells (CD16+ and/or CD56+). CD3+ T lymphocytes can be further divided into CD4+ T lymphocytes and CD8+ T lymphocytes.

BD Multitest 6-Color TBNK Reagent is a monoclonal antibody cocktail of CD3-FITC/ CD16-PE + CD56-PE/ CD45-PerCP-Cy5.5/ CD4-PE-Cy7/ CD19-APC/ CD8-APC-Cy7.

When the reagent is used to stain a known volume of whole blood, the fluorochrome-labeled antibodies in the reagent bind specifically to leucocyte surface antigens. The stained samples are treated with BD FACS™ Lysing Solution to lyse erythrocytes prior to acquisition and analysis on the BD FACSCanto or BD FACSCanto II flow cytometer. During acquisition, the cells travel past two spatially separated laser beams. The cells scatter the laser light and the cell-bound fluorochrome-labeled antibodies fluoresce. These scatter and fluorescence signals are detected by the flow cytometer and provide information about the cell's relative size, internal complexity and fluorescence intensity. During analysis by BD FACSCanto clinical software, the lymphocyte population percentages are determined. Lymphocyte population absolute counts may be determined if Ivmphocvte data from another method is manually entered.

AI/ML Overview

Here's an analysis of the provided text regarding the acceptance criteria and the study proving the device meets them:

1. Table of Acceptance Criteria and Reported Device Performance

Performance Characteristic	Acceptance Criteria	Reported Device Performance
Clinical Precision	The upper one-sided 95% confidence bound on the standard deviation (SD) for the within-device precision must be ≤2.5 on the investigational system for lymphocyte population percentages.	"Lymphocyte population percentages met the predetermined acceptance criteria: the upper one-sided 95% confidence bound on the standard deviation (SD) for the within-device precision must be ≤2.5 on the investigational system." (Excerpt implies it met the criteria, as it states it "met" them and then reiterates the criteria).
Clinical Method Comparison	The 95% confidence interval (CI) of the mean difference between the investigational and predicate systems must be within an absolute ±3% or a relative ±10% of the predicate mean, whichever is greater, for lymphocyte population percentages.	"Lymphocyte population percentages, in comparison to the predicate, met the predetermined acceptance criteria: the 95% confidence interval (CI) of the mean difference between the investigational and predicate systems must be within an absolute ±3% or a relative ±10% of the predicate mean, whichever is greater." (Excerpt implies it met the criteria).
Non-Clinical Method Comparison	The 95% CI of the mean difference between the test and predicate population shall be within +/-3% absolute or +/-10% relative to the predicate mean, whichever is greater, for lymphocyte population percentages.	"Lymphocyte population percentages, in comparison to the predicate, met the predetermined acceptance criteria: the 95% Cl of the mean difference between the test and predicate population shall be within +/-3% absolute or +/-10% relative to the predicate mean, whichever is greater." (Excerpt implies it met the criteria).
Non-Clinical Software Functionality	Predetermined functional requirements for software development (including functionality such as cytometer setup & optimization, acquisition/analysis worklist, Lab Manager, user preferences, running a QC sample, and user interface) for BD FACSCanto clinical software version 2.4.	"BD FACSCanto clinical software version 2.4 met the predetermined functional requirements for software development..." (Excerpt implies it met the criteria).
Non-Clinical File-Based Equivalency for Software	Predetermined functional requirements for providing results equivalent to the results from the previously released version of the software (BD FACSCanto clinical software version 2.2) for BD FACSCanto clinical software version 2.4.	"BD FACSCanto clinical software version 2.4 met the predetermined functional requirements for providing results equivalent to the results from the previously released version of the software, (BD FACSCanto clinical software version 2.2)." (Excerpt implies it met the criteria).

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

The document does not specify the sample size used for the clinical test sets in either the precision or method comparison studies. It also does not explicitly state the country of origin or whether the data was retrospective or prospective. It generally refers to these as "clinical studies."

For non-clinical studies (software functionality and file-based equivalency), it's implied that various tests were performed, but no sample sizes or data provenance are provided.

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

This information is not provided in the document. The device in question is a reagent and flow cytometer system for identifying cell populations, and the "ground truth" seems to be established through comparison to a predicate device and internal performance metrics, rather than expert interpretation of images or other data.

4. Adjudication Method for the Test Set

This information is not applicable or provided. The studies described involve quantitative measurements and comparisons to a predicate device and predefined statistical criteria, not subjective human adjudication of results in the way it would be used in image-based diagnostic studies.

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

There is no mention of a Multi Reader Multi Case (MRMC) comparative effectiveness study, nor is there any discussion of human readers or AI assistance. This device is an automated diagnostic assay, not an AI-powered image analysis tool for human readers.

6. If a Standalone (i.e. algorithm only without human-in-the-loop performance) was done

Yes, the performance studies described are essentially standalone in terms of the device's function. The "investigational system" (BD Multitest 6-color TBNK Reagent with BD FACSCanto/II flow cytometers) is evaluated directly for its precision and agreement with a predicate device. While a human operates the equipment, the "performance" refers to the automated output of lymphocyte percentages and counts by the system itself.

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

The primary "ground truth" implicitly used for the clinical and non-clinical method comparison studies is the predicate device (BD Multitest™ 6-Color TBNK with Trucount™ Tubes [510(k) # K060375]). The new device's performance is compared against this legally marketed and accepted predicate to establish substantial equivalence. For precision, the ground truth is statistical variability within the system itself. For software, the ground truth is its ability to meet specified functional requirements and provide equivalent results to a previous software version.

8. The Sample Size for the Training Set

The document does not mention a "training set" in the context of machine learning or AI. As this is a reagent and flow cytometry system, it operates based on established immunological principles and chemical reactions, not on algorithms that are "trained" on data in the modern AI sense.

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

As there is no mention of a "training set" in the context of an AI/machine learning model, this question is not applicable. The device's operation is based on pre-defined scientific principles and reagent characteristics.

Summary

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510(k) SUMMARY

1. Submitted By:

BD Biosciences 2350 Qume Drive San Jose, CA 95131-1807

'JUL 31 2009

Contact: Katv Campbell Regulatory Affairs Specialist Phone (408) 518-5066 Fax (408) 954-2495 katv campbell@bd.com

Submission date: April 3, 2009

2. Device Name and Classification:

a) BD Multitest™ 6-color TBNK Reagent b) 21 CFR 864.5220, Automated differential cell counter, GKZ, Class II

3. Currently Marketed Predicate Device:

BD Multitest™ 6-Color TBNK with Trucount™ Tubes [510(k) # K060375]

4. Intended Use:

BD Multitest 6-color TBNK reagent with optional BD Trucount™ tubes is a sixcolor direct immunofluorescence reagent for use with BD FACSCanto™ and BD FACSCanto™ II flow cytometers to identify and determine the percentages and absolute counts of T, B, and natural killer (NK) cells as well as the CD4 and CD8 subpopulations of T cells in peripheral blood.

BD Multitest 6-color TBNK reagent and BD Trucount tubes can be used with the BD FACS™ Loader.

5. Basic description of the device:

BD Multitest 6-Color TBNK Reagent is a monoclonal antibody cocktail of CD3-FITC/ CD16-PE + CD56-PE/ CD45-PerCP-Cy5.5/ CD4-PE-Cy7/ CD19-APC/ CD8-APC-Cy7.

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6. Comparison to the Predicate:

The content and intent of the intended use and indications of BD Multitest 6-Color TBNK Reagent, as described in its labeling, are the same as the intended use and indications of the original predicate device. The fundamental scientific technology also remains the same. In addition, BD Multitest 6-Color TBNK Reagent is substantially equivalent to the predicate (K060375) in:

· Clinical Application
Monoclonal antibody reagent composition
· Instrument used

The modification enables the use of BD Trucount tubes to be optional. The use of the reagent without BD Trucount Tubes may be more appropriate for those clinicians who need only fymphocyte population percentages or who prefer to use lymphocyte data from another method to determine lymphocyte population absolute counts.

Performance studies confirm that the devices are substantially equivalent in performance characteristics and the device modification does not raise any unresolved issues of safety or efficacy.

7. Summary of Performance Data:

Performance study data from testing supported the determination of substantial equivalence. Performance testing to support substantial equivalence included clinical and non-clinical studies. Clinical testing was done for precision and method comparison to the predicate. Non-clinical testing was done for method comparison, functionality and file-based equivalency.

Clinical Precision:

Lymphocyte population percentages met the predetermined acceptance criteria: the upper one-sided 95% confidence bound on the standard deviation (SD) for the within-device precision must be ≤2.5 on the investigational system.

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Clinical Method Comparison:

Lymphocyte population percentages, in comparison to the predicate, met the predetermined acceptance criteria: the 95% confidence interval (CI) of the mean difference between the investigational and predicate systems must be within an absolute ±3% or a relative ±10% of the predicate mean, whichever is greater.

Non-Clinical Method Comparison:

Lymphocyte population percentages, in comparison to the predicate, met the predetermined acceptance criteria: the 95% Cl of the mean difference between the test and predicate population shall be within +/-3% absolute or +/-10% relative to the predicate mean, whichever is greater.

Non-Clinical Software Functionality:

BD FACSCanto clinical software version 2.4 met the predetermined functional requirements for software development (including functionality such as cytometer setup & optimization, acquisition/analysis worklist, Lab Manager, user preferences, running a QC sample, and user interface).

Non-Clinical File-Based Equivalency for Software:

BD FACSCanto clinical software version 2.4 met the predetermined functional requirements for providing results equivalent to the results from the previously released version of the software, (BD FACSCanto clinical software version 2.2).

This 510(k) Summary is being submitted in accordance with the requirements of compliance with SMDA 1990 and 21 CFR 807.92.

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Image /page/3/Picture/0 description: The image shows a logo for the Department of Health. The logo features a stylized eagle with three stripes forming its body and wings. The text "DEPARTMENT OF HEALTH" is arranged vertically along the left side of the logo.

Food and Drug Administration 10903 New Hampshire Avenue Silver Spring, MD 20993

BD Biosciences c/o Katy Campbell Regulatory Affairs Specialist 2350 Qume Drive San Jose, California 95131-1807

JUL 81 2009

Re: K090967

Trade Name: BD Multitest™ 6-color TBNK Reagent with Trucount™ Tubes Regulation Number: 21 CFR §864.5220 Regulation Name: Automated differential cell counter Regulatory Class: Class II Product Codes: GKZ Dated: July 22, 2009 Received: July 23, 2009

Dear Ms. Campbell:

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); medical device reporting (reporting of medical device-related adverse events) (21 CFR 803); and good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820).

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Page 2 - Ms. Katy Campbell

If you desire specific advice for your device on our labeling regulation (21 CFR Part 801), please contact the Office of In Vitro Diagnostic Device Evaluation and Safety at (301) 796-5450. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding postmarket surveillance, please contact CDRH's Office of Surveillance and Biometric's (OSB's) Division of Postmarket Surveillance at (301) 796-5760. For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to

http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm for the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance.

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 ) 796-5680 or at its Internet address http://www.fda.gov/MedicalDevices/Resourcesfor You/Industry/default.htm.

Sincerely yours,

i m chan

Maria M. Chan, Ph.D. Director Division of Immunology and Hematology Devices Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health

Enclosure

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Indication for Use

510(k) Number (if known): K090967

Device Name: BD Multitest™ 6-color TBNK Reagent

Indication For Use:

BD Multitest 6-color TBNK reagent and BD Trucount tubes can be used with the BD FACS™ Loader.

Prescription Use _ X (21 CFR Part 801 Subpart D) And/Or

Over the Counter Use (21 CFR Part 801 Subpart C)

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

Concurrence of CDRH, Office of In Vitro Diagnostic Device Evaluation and Safety (OVD)

Maria M. Chen

Division Sign-Off Office of In Vitro Diagnostic Device Evaluation and Safety

510(k) K090967

Page 1 of 1

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.”