BD FACSCount CD4 reagents are used to enumerate the absolute counts of CD4 T lymphocytes and determine the percentage of lymphocytes that are CD4 T lymphocytes in unlysed whole blood (CD4 count and CD4 percentage). The reagents are for in vitro diagnostic use on a BD FACSCount instrument.

Device Description

BD FACSCount CD4 reagents are intended for use in enumerating the absolute counts of CD4 T lymphocytes and the percentage of lymphocytes that are CD4 T lymphocytes in unlysed whole blood using the BD FACSCount instrument system. The product offers a single test that requires one convenient, ready-to-use reagent tube labeled CD4. It is intended for use on a BD FACSCount instrument. The reagent kit consists of the following components: 50 reagent tubes of CD4 PE/CD14 PE-Cy5/CD15 PE-Cy5/fluorescent nuclear dye and counting reference beads, 65 reagent tube caps, One 5-mL vial of 5% formaldehyde in phosphate-buffered saline (PBS), used as fixative solution.

AI/ML Overview

Here's a breakdown of the acceptance criteria and the study results for the BD FACSCount™ CD4 Reagents, based on the provided 510(k) summary:

This device is a reagent kit for an automated differential cell counter, not an AI/ML powered device. Therefore, several of the requested categories related to AI/ML or expert adjudication in medical imaging are not applicable and will be marked as such.

Acceptance Criteria and Device Performance for BD FACSCount™ CD4 Reagents

1. Table of Acceptance Criteria and Reported Device Performance

The provided document does not explicitly state pre-defined "acceptance criteria" with numerical targets for metrics like R-squared, slope, intercept, or CV. Instead, it presents the results of equivalency studies (method comparison, precision, linearity, stability) to demonstrate that the new device performs comparably to the predicate device and within expected performance ranges for such assays.

Here's how we can infer "met acceptance criteria" based on the reported results, assuming the FDA reviewed these results and granted substantial equivalence:

Performance Metric	Acceptance Criteria (Inferred from granted clearance)	Reported Device Performance	Device Meets Criteria?
Method Comparison:
CD4 Absolute Count (R²)	Demonstrated strong correlation (R² close to 1) with the predicate device.	0.981	Yes
CD4 Absolute Count (Slope)	Demonstrated good agreement (slope close to 1) with the predicate device.	0.971	Yes
CD4 Absolute Count (Intercept)	Demonstrated minimal bias (intercept close to 0) compared to the predicate device.	12.695	Yes
CD4 Percentage (R²)	Demonstrated strong correlation (R² close to 1) with the predicate device.	0.99	Yes
CD4 Percentage (Slope)	Demonstrated good agreement (slope close to 1) with the predicate device.	0.999	Yes
CD4 Percentage (Intercept)	Demonstrated minimal bias (intercept close to 0) compared to the predicate device.	-0.391	Yes
Precision:
CD4 Abs Count (Low Control CV) (Within Device/Run)	Acceptable within-device and within-run variability for low control. (Typically below 5-10% for flow cytometry)	Within Device: 4.82% Within Run: 4.04%	Yes
CD4 Abs Count (Normal Control CV) (Within Device/Run)	Acceptable within-device and within-run variability for normal control. (Typically below 5-10% for flow cytometry)	Within Device: 4.28% Within Run: 3.46%	Yes
CD4 Percentage (Low Control CV) (Within Device/Run)	Acceptable within-device and within-run variability for low control.	Within Device: 0.38% Within Run: 0.35%	Yes
CD4 Percentage (Normal Control CV) (Within Device/Run)	Acceptable within-device and within-run variability for normal control.	Within Device: 1.28% Within Run: 1.15%	Yes
Linearity	Demonstrated linearity across the specified reportable range.	Assessed and observed to be linear within 50 - 5000 cells/ulCD4+ absolute count range.	Yes
Stain Stability	Demonstrated stability for stained samples up to a certain time.	Stable up to 48 hours of age of stain.	Yes
Reagent Stability	Demonstrated shelf-life stability for the reagents.	Stable up to 15 months.	Yes

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

Test Set Sample Size:
- Method Comparison:
  - CD4 Absolute Count: n = 101 samples
  - CD4 Percentage: n = 99 samples
- Precision: Not explicitly stated as a number of individual patient samples, but rather as results from "low control" and "normal control" measurements across multiple runs/devices.
- Linearity, Stain Stability, Reagent Stability: Specific sample sizes (e.g., number of replicates or distinct samples used for dilution series) are not provided.
Data Provenance: Not explicitly stated in the summary document. It's common for such studies to be conducted internally by the manufacturer or through clinical sites, but specific country of origin or whether it was retrospective/prospective is not detailed here. Given the nature of a 510(k) submission, it's generally assumed to be prospective data collection, but this is not confirmed.

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

Not applicable (N/A) for this type of device. This device is an in vitro diagnostic reagent kit for automated cell counting. The "ground truth" for comparison is typically established by the predicate device and/or reference methods, not by human experts adjudicating images or clinical findings.

4. Adjudication Method for the Test Set

Not applicable (N/A). As explained above, for laboratory assays, "adjudication" in the sense of multiple experts reviewing and reaching consensus on findings is not a typical methodology. Performance is assessed against a predicate device or established reference methods.

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

No, an MRMC comparative effectiveness study was not done. This device is an in vitro diagnostic reagent kit designed for automated analysis, not an AI system assisting human readers. Therefore, the concept of human readers improving with or without AI assistance is not relevant here.

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

Yes, in spirit, a standalone performance was done for the device system. The BD FACSCount™ CD4 Reagents are used with the BD FACSCount instrument, which performs automated analysis. The "algorithm" in this context is the instrument's automated processing and counting of labeled cells. The performance data presented (method comparison, precision, linearity, etc.) reflects the standalone performance of this integrated system (reagents + instrument) in enumerating CD4 cells. There is no human "in-the-loop" decision-making for the actual cell counting process with this automated system.

7. The Type of Ground Truth Used

Comparison to a Predicate Device: The primary "ground truth" or reference for demonstrating substantial equivalence was the performance of the BD Tritest CD3/CD4/CD45 with and without BD Trucount absolute count tubes on a BD FACSCalibur instrument (the predicate device).
Reference Intervals/Expected Performance: For precision and linearity, the "ground truth" is implied by expected biological ranges, established control values, and the design of dilution series to assess assay performance across its claimed dynamic range.

8. The Sample Size for the Training Set

Not applicable (N/A) in the context of AI/ML training. This device is a reagent kit for a traditional analytical instrument. There is no "training set" in the sense of data used to train an AI/ML algorithm. The "training" of the system (instrument and reagents) would involve internal development and optimization processes by the manufacturer, but not in the AI/ML paradigm.

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

Not applicable (N/A). As there is no AI/ML training set, the establishment of ground truth for such a set is irrelevant. The "ground truth" reference for the general development and calibration of such assays would derive from established laboratory techniques, reference materials, and predicate device performance during the product development lifecycle.

Summary

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Kofi2i3

510(k) Summary

1.0: Submitted By:

AUG 1 4 2008

BD Biosciences 2350 Qume Drive San Jose, CA 95131

Contact: Nobuko Nakajima Senior Regulatory Specialist (408) 954-4109 (408) 954-2495 (FAX) nobuko nakajima@bd.com

Submission Date: April 28, 2008

2.0: Device Name:

a) BD FACSCount™ CD4 Reagents b) 21CFR 862.5220Automated Differential Cell Counter (GKZ Class II)

3.0: Intended Use:

4.0: Basic description of the device:

The reagent kit consists of the following components:

50 reagent tubes of CD4 PE/CD14 PE-Cy5/CD15 PE-Cy5/fluorescent nuclear dye and . counting reference beads
. 65 reagent tube caps
One 5-mL vial of 5% formaldehyde in phosphate-buffered saline (PBS), used as fixative . solution

5.0: Predicate Device:

BD FACSCount CD4 Reagents is substantially equivalent to BD Tritest CD3/CD4/CD45 with and without BD Trucount absolute count tubes (K071143 and K071141) for the enumerating the absolute counts of CD4 T lymphocytes and the percentage of lymphocytes that are CD4 T lymphocytes in unlysed whole blood.

BD Biosciences Premarket Notification BD FACSCount CD4 Reagents

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6.0 Comparison to the Predicate:

Characteristic	BD TriTEST CD3/CD4/CD45 with andwithout BD Trucount absolute counttubes on BD FACSCalibur(Predicate)	BD FACSCount CD4 Reagents onBD FACSCount(New)
Intended Use	BD TriTEST CD3/CD4/CD45 is a threecolor direct immunofluorescence reagentfor use with a suitably equipped flowcytometer to identify and determine thepercentages and absolute counts of maturehuman T lymphocytes (CD3+),helper/inducer (CD3+CD4+) Tlymphocytes in erythrocyte lysed wholeblood. When used with BD Trucounttubes, absolute counts of these populationscan be enumerated from a single tube.This BD Tritest reagent and BD Trucounttubes can be used with the BDFACSLoader. The reagent can be usedwith or without an isotype control.	BD FACSCount CD4 Reagents are twocolor direct immunofluorescence reagentfor identifying and determining absolutecounts in cells/ul and percentage ofCD4+ T lymphocytes in unlysed wholeblood.
Deviceclassification andproduct code	Class II81 GKZRegulation 21 CFR §864.5220	Same
Reagent	BD TriTESTCD3FITC/CD4PE/CD45PerCP	BD FACSCount CD4 ReagentsCD4PE/CD14PE-Cy5/CD15PECy5/fluorescent nuclear dy
Absolute countbeads	Trucount Absolute Count beads	Known number of reference beadsincluded in reagent
ControlBeads	None	BD FACSCount Controls(low/mid/high)
Sample type	Whole blood preserved with EDTA,heparin, or ACD-Solution A	Whole blood preserved with EDTAonly
System electronics	Analog	Same
Fluorescence Scale(Display)	Calibur 1024 log scale or 104 linear scale	N/A - Customer does not see the dot-plot
Cytometer setup	Uses FACSComp software with BDCalibriteTM Beads to set up FL2.	None – no customer set up required
Sample Analysis:	Automatic analysis. User is able to adjustthe gating to optimize.	Automatic analysis with no userintervention
Dynamic Range	68 - 7.2x103 cells/ul CD4/CD3 positivecells	CD4 absolute count of: 50-5000cells/ulCD4 percentage of : 5-65%
Results	Samples are reported as CD4/CD3positive cells/ul and CD4/CD3 %positives of Lymphocytes	Samples are reported as CD4 cells/uland CD4% of Lymphocytes

Similarities and Differences:

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7.0: Summary of Performance Data:

Equivalency for the candidate product has been demonstrated through method comparison, precision, linearity stain stability, and reagent stability studies.

A) Summary of Method Comparison study results:

Parameter	n	R2	Slope	Intercept
CD4 Absolute Count (cells/uL)	101	0.981	0.971	12.695
CD4 Percentage (%)	99	0.99	0.999	-0.391

B) Summary of System Precision study results:

Within-device and within-run precision of CD4 absolute counts (cells/uL)
	Comments of the Real Call College of the Children and Children and

	Low control CV(cell/ul)	Normal control CV(cells/ul)
Within device	4.82	4.28
Within run	4.04	3.46

Within-device and within-run precision of CD4 percentage (cells/uL)

	Low control CV(cell/ul)	Normal control CV(cells/ul)
Within device	0.38	1.28
Within run	0.35	1.15

C) Summary of System Linearity study results:

Linearity was assessed and observed to be linear within the reportable CD4+ absolute count range (50 - 5000 cells/ul).

D) Summary of Stained Sample Stability (Age of Stain) study:

Age of blood and age of stained sample were assessed and observed to be stable up to 24 hours of age of blood and up to 48 hours of age of stain.

E) Summary of Reagent Stability (Shelflife) study:

Reagents were assessed and the Kit was observed to be stable up to 15 month. Expiration dating may be extended in the future if ongoing product stability testing supports the extension.

This Summary of safety and effectiveness is being submitted in accordance with the requirements of compliance with SMDA 1990 and 21 CFR807.92.

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DEPARTMENT OF HEALTH & HUMAN SERVICES

Image /page/3/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a stylized caduceus symbol, which is a staff with two snakes coiled around it, and the words "DEPARTMENT OF HEALTH & HUMAN SERVICES USA" arranged in a circular pattern around the symbol. The logo is black and white.

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

AUG 1 4 2008

BD Biosciences c/o Mr. Nobuko Nakajima Senior Regulatory Affairs Specialist 2350 Qume Drive San Jose, CA 95131

Re: K081213

Trade/Device Name: BD FACSCount™ CD4 Reagents Regulation Number: 21 CFR 864.5220 Regulation Name: Automated differential cell counter Regulatory Class: Class II Product Code: GKZ Dated: July 30, 2008 Received: July 31, 2008

Dear Mr. Nakajima:

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); and good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820). This letter will allow you to begin marketing your device as described in your Section 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.

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Page 2

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 (240) 276-0450. Also, please note the regulation entitled. "Misbranding by reference to premarket notification" (21CFR 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 (240) 276-3474. For questions regarding the reporting of device adverse events (Medical Device Reporting (MDR)), please contact the Division of Surveillance Systems at (240) 276-3464. 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 (240) 276-3150 or at its Internet address http://www.fda.gov/cdrh/industry/support/index.html.

Sincerely yours,

m chan

Maria M. Chan, Ph.D. Acting Division 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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Indications for Use

510(k) Number (if known): K081213

Device Name: BD FACSCount™ CD4 Reagents

Indications for Use:

Prescription Use × (Part 21 CFR 801 Subpart D)

AND/OR

Over-The-Counter Use (21 CFR 801 Subpart C)

ﺗﻢ ﺍ

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

Concurrence of CDRH, Office of Device Evaluation (ODE)

Moria M Chan
Division Sign-Off

Office of In Vitro Diganostic Device Evaluation and Safety

Kafr/2-13

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.”