(91 days)
Not Found
No
The summary describes a standard flow cytometry system and its associated reagents and software for immunophenotyping. There is no mention of AI, ML, or any related technologies in the intended use, device description, or performance studies. The analysis relies on established methods of light scatter and fluorescence detection.
No.
The device is described as an in vitro diagnostic (IVD) device used for immunophenotyping to assess immune status. It is for diagnostic purposes, not for treating or preventing disease.
Yes
The "Intended Use / Indications for Use" section explicitly states, "The BD FACSLyric™ flow cytometer is intended for use as an in vitro diagnostic device for immunophenotyping..." and "It is intended for use with in vitro diagnostic (IVD) assays and software that are indicated for use with the instrument." The text also describes its use in the "immunological assessment of normal individuals, and patients having, or suspected of having, immune deficiency," which directly relates to diagnosing conditions.
No
The device description explicitly lists hardware components, including the FACSLyric Flow Cytometer itself, which is a physical instrument. While it includes software (FACSuite Clinical Software), it is not solely software.
Yes, the BD FACSLyric™ flow cytometer is an IVD (In Vitro Diagnostic) device.
This is explicitly stated in the "Intended Use / Indications for Use" section:
"The BD FACSLyric™ flow cytometer is intended for use as an in vitro diagnostic device for immunophenotyping..."
N/A
Intended Use / Indications for Use
The BD FACSLyric flow cytometer is intended for use as an in vitro diagnostic device for immunophenotyping using up to six fluorescence detection channels and two light scatter channels using a blue (488-nm) and a red (640-nm) laser. It is intended for use with in vitro diagnostic (IVD) assays and software that are indicated for use with the instrument.
BD Multitest™ 6-color TBNK, BD Multitest™ IMK kit, BD Multitest™ CD3/CD8/CD45/CD4, and BD Multitest™ CD3/CD16+CD56/CD45/CD19, all with optional BD Trucount™ tubes, are intended for use on the BD FACSLyric flow cytometer with peripheral whole blood for immunophenotyping. These reagents are indicated for use in the immunological assessment of normal individuals, and patients having, or suspected of having, immune deficiency. These reagents determine the percentages and absolute counts of the following mature human lymphocyte subsets:
BD Multitest 6-color TBNK with optional BD Trucount tubes
• T lymphocytes (CD3+)
• B lymphocytes (CD19+)
• Natural killer (NK) lymphocytes (CD3-CD16+ and/or CD56+)
• Helper/inducer T lymphocytes (CD3+CD4+)
• Suppressor/cytotoxic T lymphocytes (CD3+CD8+)
BD Multitest IMK kit with optional BD Trucount tubes
• T lymphocytes (CD3+)
• B lymphocytes (CD19+)
• Natural killer (NK) lymphocytes (CD3-CD16+ and/or CD56+)
• Helper/inducer T lymphocytes (CD3+CD4+)
• Suppressor/cytotoxic T lymphocytes (CD3+CD8+)
BD Multitest CD3/CD8/CD45/CD4 with optional BD Trucount tubes
• T lymphocytes (CD3+)
• Suppressor/cytotoxic T lymphocytes (CD3+CD8+)
• Helper/inducer T lymphocytes (CD3+CD4+)
BD Multitest CD3/CD16+CD56/CD45/CD19 with optional BD Trucount tubes
• T lymphocytes (CD3+)
• Natural killer (NK) lymphocytes (CD3-CD16+ and/or CD56+)
• B lymphocytes (CD3-CD19+)
Product codes (comma separated list FDA assigned to the subject device)
OYE
Device Description
The BD FACSLyric Flow Cytometer consists of the following components.
- FACSLyric Flow Cytometer (3-1, 4-2, 4-2-2 and 4-3-3 optical configurations)
- FACSuite Clinical Software
- Multitest 6-Color Assay Modules
- Multitest 4-Color Assay Modules
- FC Beads 7-Color Kit
- CS&T Beads
- Multitest 6-Color TBNK
- Multitest IMK Kit
- Multitest CD3/CD8/CD45/CD4
- Multitest CD3/CD16+CD56/CD45/CD19
- Multi-Check Control
- Multi-Check CD4 Low Control
- Trucount Tubes
- Optional FACS Universal Loader
In accordance with FDA Guidance for Industry and FDA Staff, Bundling Multiple Devices or Multiple Indications in a Single Submission, dated June 22, 2007, four Multitest assays with the instrument, beads and process controls are bundled within this submission.
The FACSLyric System with Multitest Reagents is intended for the immunological assessment of normal individuals, and patients having, or suspected of having, immune deficiency using flow cytometry applications.
The system is an immunofluorescence assay system for identification and enumeration of lymphocyte subsets in peripheral whole blood. When blood is added to the monoclonal antibody reagent, the fluorochrome-labeled antibodies in the reagent bind specifically to lymphocvte surface antigens. During acquisition, the cells travel past one or more laser beams in a single file and scatter the laser light. The stained cells fluoresce. The scatter and fluorescence light is detected by the flow cytometer, separated by dichroic mirrors and optical filters, and then quantified with photomultiplier tubes (PMTs) to determine the percent lymphocyte of particular cell populations.
Multiple monoclonal antibodies each labeled with a different fluorochrome are contained within one reagent tube to simultaneously identify multiple lymphocyte subset populations. The use of Trucount tubes provides the absolute number of the fluorochrome-labeled antibody bound cells.
The FACSLyric System with Multitest Reagents is intended for Prescription Use Only and will be labeled "Rx Only".
Mentions image processing
Not Found
Mentions AI, DNN, or ML
Not Found
Input Imaging Modality
Flow Cytometry
Anatomical Site
Not Found
Indicated Patient Age Range
Not Found
Intended User / Care Setting
Prescription Use (Part 21 CFR 801 Subpart D)
Description of the training set, sample size, data source, and annotation protocol
Not Found
Description of the test set, sample size, data source, and annotation protocol
Not Found
Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)
Bench Performance Summary:
-
Intra-instrument Optical Configuration Equivalency
- Objective: To demonstrate system level performance equivalency across the 3-1 (4-color), 4-2 (6-color), 4-2-2 (8-color), and 4-3-3 (10-color) optical configurations of the FACSLyric flow cytometer as measured by QC and setup performance parameters generated utilizing CS&T beads and FC beads.
- Results: System level optical equivalency was demonstrated between the four configurations (3-1, 4-2, 4-2-2 and 4-3-3) of the FACSLyric system.
-
Inter-instrument Optical Configuration Equivalency
- Standard/Reference: CLSI EP09-A3, Measurement Procedure Comparison and Bias Estimation Using Patient Samples: Approved Guideline- Third Edition
- Objective: To demonstrate performance equivalency between the 3-1 (4-color), 4-2 (6-color), 4-2-2 (8-color), and 4-3-3 (10-color) optical configurations of the FACSLyric flow cytometer through testing multiple instruments of different configurations (inter-instrument) using patient and normal donor samples stained with Multitest IMK kit and Multitest 6-Color TBNK in Trucount tubes.
- Results: The performance equivalency of the 6 IVD channels between the 3-1, 4-2, 4-2-2 and 4-3-3 optical configurations of the FACSLyric flow cytometer have been demonstrated.
-
Method Comparison
- Standard/Reference: CLSI EP09-A3, Measurement Procedure Comparison and Bias Estimation Using Patient Samples; Approved Guideline- Third Edition
- Objective:
- To determine the method bias between the FACSLyric system with Multitest reagents and the FACSCanto II system with Multitest reagents on the determination of CD3+, CD3+CD4+, CD3+CD8+, CD19+ and CD16+56+ percentage and absolute counts.
- To demonstrate equivalency between FACSLyric Universal Loader (UL) acquisition and FACSLyric manual acquisition when using the Multitest IMK kit and Multitest 6-Color TBNK with Trucount tubes in the determination of CD3+, CD3+CD4+, CD3+CD8+, CD19+ and CD16+56+ percentage and absolute counts.
- Results: The method bias between the FACSLyric and the FACSCanto II, in the determination of CD3+, CD3+CD4+, CD3+CD8+, CD19+ and CD16+56+ percentage and absolute counts, met the acceptance criteria using the Multitest IMK kit and Multitest 6-Color TBNK with Trucount tubes. In addition, equivalency between the FACSLyric UL acquisition and Manual acquisition was demonstrated.
-
Within-site Precision
- Standard/Reference: CLSI EP05-A3, Evaluation of Precision of Quantitative Measurement Procedures: Approved Guideline-Third Edition.
- Objective: To evaluate the within-site precision performance of FACSLyric system using the Multitest IMK kit and Multitest 6-Color TBNK with Trucount tubes.
- Results: All acceptance criteria were met. The within-site precision performance of FACSLyric system using the Multitest IMK kit and Multitest 6-Color TBNK with Trucount tubes satisfied the within-run and total precision performance requirements.
-
Whole Blood Repeatability
- Standard/Reference: CLSI EP05-A3, Evaluation of Precision of Quantitative Measurement Procedures; Approved Guideline-Third Edition.
- Objective: To verify repeatability performance across all the FACSLyric instruments of different configurations, using whole blood from patient and normal donor samples, stained with the Multitest IMK kit and Multitest 6-Color TBNK with Trucount tubes.
- Results: Repeatability performance was demonstrated across all the instruments with different configurations. All lymphocyte subsets met %CV and SD acceptance criteria.
-
Linearity
- Standard/Reference: CLSI EP6-A, Evaluation of the Linearity of Quantitative Measurement Procedures: A Statistical Approach: Approved Guideline.
- Objective: To evaluate the linear range of the FACSLyric system using the Multitest IMK kit and Multitest 6-Color TBNK with Trucount tubes.
- Results: Acceptable linear ranges have been established for each lymphocyte subset for each of the Multitest reagents on FACSLyric system.
-
Sample Carryover
- Standard/Reference: CLSI H26-A2, Validation, Verification, and Quality Assurance of Automated Hematology Analyzers; Approved Standard- Second Edition
- Objective: To determine the percent sample carryover based on acquisition of three highly concentrated samples immediately followed by acquisition of three low concentrated samples on FACSLyric system.
- Results: All the results met the acceptance criteria of system carryover less than or equal to 0.1% for low carryover and less than or equal to 0.5% for standard carryover on all three FACSLyric instruments. To meet the low carryover requirement the results demonstrated that only a single SIT flush was required.
-
Reagent Carryover
- Standard/Reference: CLSI H26-A2 Validation, Verification, and Quality Assurance of Automated Hematology Analyzers; Approved Standard- Second Edition.
- Objective: To verify the capability of the FACSLyric system to acquire samples with minimal reagent carryover.
- Results: Results met the acceptance criteria were met. The amount of reagent being carried over is found to be well below the amount of reagent required for effective staining of the sample.
-
Detection Capability of LoB and LoD
- Standard/Reference: CLSI EP17-A2, Evaluation of Detection Capability for Clinical Laboratory Measurement Procedures; Approved Guideline-Second Edition.
- Objective: To evaluate the limit of blank (LoB) and limit of detection (LoD) of the FACSLyric system with Multitest IMK kit and Multitest 6-Color TBNK with Trucount tubes.
- Results: The detection capability parameters for the limit of blank (LoB) and limit of detection (LoD) of the FACSLyric system were established for BD Multitest reagents. For CD4 lymphocyte subset absolute counts of each of the reagents, the established LoB and LoD were less than 50 cells/µL.
-
Detection Capability of LoQ
- Standard/Reference: CLSI EP17-A2, Evaluation of Detection Capability for Clinical Laboratory Measurement Procedures; Approved Guideline-Second Edition.
- Objective: To evaluate the limit of quantitation (LoQ) of the FACSLyric system using Multitest IMK kit and Multitest 6-Color TBNK, both with Trucount tubes.
- Results: The LoQ of the FACSLyric system with Multitest reagents was established for the CD3+, CD3+CD4+, CD3+CD8+, CD19+, CD16+CD56+ and CD45+ lymphocyte subsets. The acceptance criteria were met and the LOQ is less than 50 cells/µL for CD4 lymphocyte subset absolute counts.
-
Setup and QC Performance
- Objective: To verify that Setup & QC Performance of the FACSLyric system meets the pre-defined specifications.
- Results: All the Setup & QC performance results of the FACSLyric system met the acceptance criteria.
-
Setup and QC Stability
- Objective: To verify the stability of system level Setup & QC on the FACSLyric system.
- Results: All the system level Setup & QC stability performance results on the FACSLyric system met the pre-defined specifications.
Clinical Performance Summary:
-
Method Comparison
- Standard/Reference: CLSI EP09-A3, Measurement Procedure Comparison and Bias Estimation Using Patient Samples; Approved Guideline- Third Edition
- Testing Approach: To evaluate performance equivalence of the FACSLyric system and the FACSCanto II system on the determination of lymphocyte subsets using the Multitest 6-Color TBNK and Multitest IMK kit, both with Trucount tubes, using remnant, de-linked patient specimens.
- Results: A total of 332 specimens were enrolled for testing with Multitest 6-Color TBNK (297 evaluable), and 368 specimens were enrolled for Multitest IMK kit (336 evaluable) at 5 clinical sites. The acceptance criteria for all lymphocyte subsets were met for the FACSLyric system. The differences of the results between all the specimens and the non-manipulated specimens were very minimal, and no bias trend was observed. Additional analysis per site and by different EDTA anticoagulant formulations (EDTA-K2 vs EDTA-K3) in the blood collection tubes also showed minimal difference with no trend observed.
-
Inter-laboratory Reproducibility
- Standard/Reference: CLSI EP05-A3, Evaluation of Precision of Quantitative Measurement Procedures; Approved Guideline-Third Edition.
- Testing Approach: To evaluate inter-laboratory reproducibility for the FACSLyric system on the determination of lymphocyte subsets using the Multitest 6-Color TBNK and Multitest IMK kit in Trucount tubes with a single lot of Streck CD-Chex Plus process control material.
- Results: Inter-laboratory reproducibility was carried out at four clinical sites. The variability for within run, between run, between day, between site and total precision per reagent and lymphocyte subset was evaluated. The 97.5% one-sided confidence interval (CI) on the within run and total precision was estimated and compared to the acceptance criteria. (Partial text, cutoff in original document)
-
Reference Intervals
- Standard/Reference: CLSI EP28-A3c How to Define and Determine Reference Intervals in the Clinical Laboratory, Approved Guideline- Second Edition.
- Testing Approach: To re-establish the reference intervals of a normal male and female adult cohort, free of hematological abnormality, using the FACSLyric system for the Multitest 6-Color TBNK and Multitest IMK kit, both with Trucount tubes, on determination of lymphocyte subsets using prospectively procured and de-linked donor specimens at one study site.
- Results: A total of 136 subjects were enrolled (134 evaluable for Multitest 6-Color TBNK and 130 evaluable for Multitest IMK kit) from one clinical site. Reference Intervals for all lymphocyte subsets in the Multitest 6-Color TBNK and Multitest IMK kit were established for the FACSLyric system. Differences were observed between genders, but these differences are not clinically significant.
-
Specimen Stability
- Testing Approach: To generate data to support stability of venous whole blood with EDTA anticoagulant when testing the Multitest 6-Color TBNK and Multitest IMK kit, both with Trucount tubes, on the FACSLyric system using prospectively procured and de-linked patient specimens from at least two study sites.
- Results: A total of 227 specimens were enrolled for each of the reagents from the two clinical sites. 180 specimens were evaluable for Multitest 6-Color TBNK and 186 were evaluable for Multitest IMK kit. The results from the study support the claim of up to 24 hours Age of Blood and 6 hours Age of Stain for Multitest 6-Color TBNK, and up to 48 hours Age of Blood and 24 hours Age of Stain for Multitest IMK kit (include Multitest CD3/CD8/CD45/CD4 and Multitest CD3/CD16+CD56/CD45/CD19) on FACSLyric system.
Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)
Not Found
Predicate Device(s): If the device was cleared using the 510(k) pathway, identify the Predicate Device(s) K/DEN number used to claim substantial equivalence and list them here in a comma separated list exactly as they appear in the text. List the primary predicate first in the list.
K141468, K062087, K040026, K090967, K980858, K974360, K961610, K982231, K970836
Reference Device(s): Identify the Reference Device(s) K/DEN number and list them here in a comma separated list exactly as they appear in the text.
Not Found
Predetermined Change Control Plan (PCCP) - All Relevant Information for the subject device only (e.g. presence / absence, what scope was granted / cleared under the PCCP, any restrictions, etc).
Not Found
§ 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.”
0
Image /page/0/Picture/1 description: The image shows the seal of the Department of Health & Human Services - USA. The seal is circular and contains the department's name around the perimeter. In the center of the seal is an abstract symbol that resembles a stylized caduceus or a series of human profiles.
Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002
August 28, 2017
Becton, Dickinson and Company Li Zhou Manager, Regulatory Affairs, BD Biosciences 2350 Qume Drive San Jose. CA 95131
Re: K170974
Trade/Device Name: BD FACSLyric™ Flow Cytometer Regulation Number: 21 CFR 864.5220 Regulation Name: Automated differential cell counter Regulatory Class: II Product Code: OYE Dated: March 31, 2017 Received: April 03, 2017
Dear Ms. Zhou:
This letter corrects our substantially equivalent letter of July 3, 2017.
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. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.
If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. 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); good manufacturing practice requirements
1
as set forth in the quality systems (OS) regulation (21 CFR Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.
If vou desire specific advice for your device on our labeling regulation (21 CFR Part 801 and 809), please contact the Division of Industry and Consumer Education at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address
http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR Part 807.97). 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 Industry and Consumer Education at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address
http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm.
Sincerely,
Leonthena R. Carrington -S
Lea Carrington Director Division of Immunology and Hematology Devices Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health
Enclosure
2
Indications for Use
510(k) Number (if known) K170974
Device Name
BD FACSLyric™ Flow Cytometer
Indications for Use (Describe)
The BD FACSLyric™ flow cytometer is intended for use as an in vitro diagnostic device for immunophenotyping using up to six fluorescence detection channels and two light scatter channels using a blue (488-nm) and a red (640-nm) laser. It is intended for use with in vitro diagnostic (IVD) assays and software that are indicated for use with the instrument.
BD Multitest™ 6-color TBNK, BD Multitest™ IMK kit, BD Multitest™ CD3/CD8/CD45/CD4, and BD Multitest™ CD3/CD16+CD56/CD45/CD19, all with optional BD Trucount™ tubes, are intended for use on the BD FACSLyric flow cytometer with peripheral whole blood for immunophenotyping. These reagents are indicated for use in the immunological assessment of normal individuals, and patients having, or suspected of having, immune deficiency. These reagents determine the percentages and absolute counts of the following mature human lymphocyte subsets:
BD Multitest 6-color TBNK with optional BD Trucount tubes
- · T lymphocytes (CD3+)
- · B lymphocytes (CD19+)
- · Natural killer (NK) lymphocytes (CD3-CD16+ and/or CD56+)
- · Helper/inducer T lymphocytes (CD3+CD4+)
- · Suppressor/cytotoxic T lymphocytes (CD3+CD8+)
BD Multitest IMK kit with optional BD Trucount tubes
- · T lymphocytes (CD3+)
- · B lymphocytes (CD19+)
- · Natural killer (NK) lymphocytes (CD3-CD16+ and/or CD56+)
- · Helper/inducer T lymphocytes (CD3+CD4+)
- · Suppressor/cytotoxic T lymphocytes (CD3+CD8+)
BD Multitest CD3/CD8/CD45/CD4 with optional BD Trucount tubes
- · T lymphocytes (CD3+)
- · Suppressor/cytotoxic T lymphocytes (CD3+CD8+)
- · Helper/inducer T lymphocytes (CD3+CD4+)
BD Multitest CD3/CD16+CD56/CD45/CD19 with optional BD Trucount tubes
- · T lymphocytes (CD3+)
- · Natural killer (NK) lymphocytes (CD3-CD16+ and/or CD56+)
- · B lymphocytes (CD3-CD19+)
3
Type of Use (Select one or both, as applicable)
X Prescription Use (Part 21 CFR 801 Subpart D)
| Over-The-Counter Use (21 CFR 801 Subpart C)
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4
Section 5 510(k) Summary
This bundled 510(k) summary is being provided in accordance with the requirements of the Safe Medical Devices Act of 1990 and 21 CFR 807.92.
Date of Summary: March 31, 2017
5.1 Submitted By
BD Biosciences 2350 Oume Drive San Jose, CA 95131-1807 USA
| Contact: | Li Zhou
Manager, Regulatory Affairs |
|------------|----------------------------------------|
| Telephone: | (408) 954-2099 |
| Fax: | (408) 954-2347 |
| Email: | li.zhou2@BD.com |
5.2 Device
Trade Name/Device Name: BD FACSLyric™ Flow Cytometer
Classification: Class II Device Classification: Flow Cytometric Reagents and Accessories Regulation Description: Automated Differential Cell Counter Regulation Medical Specialty: Hematology Product Code: OYE Regulation Number: 21 CFR 864.5220
5.3 Predicate Device
The predicate device is BD FACSCanto™ II system with BD Multitest™ reagents that consists of the following:
- FACSCanto II flow cytometer (4-2, 4-2-2 and 5-3 optical configurations) (K141468 ● and K062087)
- . FACSCanto Clinical Software (Multitest 6-Color and 4-Color assays are included as panels within FACSCanto Clinical software) (K141468 and K062087)
- FACS 7-Color Setup Beads (K040026) ●
- Multitest 6-Color TBNK (K090967)
- Multitest IMK Kit (K980858)
- Multitest CD3/CD8/CD45/CD4 (K974360)
- Multitest CD3/C16+CD56/CD45/CD19 (K980858)
- Multi-Check Control (K961610) ●
- Multi-Check CD4 Low Control (K982231) ●
- Trucount Tubes (K970836)
- Optional FACS Loader (K141468 and K062087)
5
5.4 Device Description
The BD FACSLyric Flow Cytometer consists of the following components.
- FACSLyric Flow Cytometer (3-1, 4-2, 4-2-2 and 4-3-3 optical configurations) ●
- FACSuite Clinical Software ●
- Multitest 6-Color Assay Modules ●
- Multitest 4-Color Assay Modules ●
- FC Beads 7-Color Kit
- CS&T Beads
- Multitest 6-Color TBNK
- Multitest IMK Kit
- . Multitest CD3/CD8/CD45/CD4
- Multitest CD3/CD16+CD56/CD45/CD19 ●
- . Multi-Check Control
- . Multi-Check CD4 Low Control
- . Trucount Tubes
- Optional FACS Universal Loader ●
In accordance with FDA Guidance for Industry and FDA Staff, Bundling Multiple Devices or Multiple Indications in a Single Submission, dated June 22, 2007, four Multitest assays with the instrument, beads and process controls are bundled within this submission.
The FACSLyric System with Multitest Reagents is intended for the immunological assessment of normal individuals, and patients having, or suspected of having, immune deficiency using flow cytometry applications.
The system is an immunofluorescence assay system for identification and enumeration of lymphocyte subsets in peripheral whole blood. When blood is added to the monoclonal antibody reagent, the fluorochrome-labeled antibodies in the reagent bind specifically to lymphocvte surface antigens. During acquisition, the cells travel past one or more laser beams in a single file and scatter the laser light. The stained cells fluoresce. The scatter and fluorescence light is detected by the flow cytometer, separated by dichroic mirrors and optical filters, and then quantified with photomultiplier tubes (PMTs) to determine the percent lymphocyte of particular cell populations.
Multiple monoclonal antibodies each labeled with a different fluorochrome are contained within one reagent tube to simultaneously identify multiple lymphocyte subset populations. The use of Trucount tubes provides the absolute number of the fluorochrome-labeled antibody bound cells.
The FACSLyric System with Multitest Reagents is intended for Prescription Use Only and will be labeled "Rx Only".
6
5.5 Indications for Use
5.6.1 BD FACSLvric Flow Cytometer
The BD FACSLyric™ flow cytometer is intended for use as an in vitro diagnostic device for immunophenotyping using up to six fluorescence detection channels and two light scatter channels using a blue (488-nm) and a red (640-nm) laser. It is intended for use with in vitro diagnostic (IVD) assays and software that are indicated for use with the instrument.
BD Multitest™ 6-color TBNK, BD Multitest™ IMK kit, BD Multitest™ CD3/CD8/CD45/CD4. and BD Multitest™ CD3/CD16+CD56/CD45/CD19. all with optional BD Trucount™ tubes, are intended for use on the BD FACSLyric flow cytometer with peripheral whole blood for immunophenotyping. These reagents are indicated for use in the immunological assessment of normal individuals, and patients having, or suspected of having, immune deficiency. These reagents determine the percentages and absolute counts of the following mature human lymphocyte subsets:
BD Multitest 6-color TBNK with optional BD Trucount tubes
- T lymphocytes (CD3+) ●
- B lymphocytes (CD19*) .
- . Natural killer (NK) lymphocytes (CD3-CD16+ and/or CD56*)
- . Helper/inducer T lymphocytes (CD3CD4)
- Suppressor/cytotoxic T lymphocytes (CD3CD8)
BD Multitest IMK kit with optional BD Trucount tubes
- T lymphocytes (CD3+) .
- . B lymphocytes (CD19*)
- Natural killer (NK) lymphocytes (CD3-CD16+ and/or CD56*)
- Helper/inducer T lymphocytes (CD3+CD4*) .
- Suppressor/cytotoxic T lymphocytes (CD3CD8) .
BD Multitest CD3/CD8/CD45/CD4 with optional BD Trucount tubes
- T lymphocytes (CD3+)
- Suppressor/cytotoxic T lymphocytes (CD3+CD8+) .
- . Helper/inducer T lymphocytes (CD3+CD4+)
BD Multitest CD3/CD16+CD56/CD45/CD19 with optional BD Trucount tubes
- T lymphocytes (CD3+) ●
- Natural killer (NK) lymphocytes (CD3-CD16+ and/or CD56+)
- B lymphocytes (CD3-CD19+) .
7
5.6.2 BD FC beads 7-color kit
The BD™ FC beads 7-color kit (BD FC beads), in conjunction with BD FACSuite™ Clinical software and BD™ CS&T beads, are used to establish fluorescence compensation for the BD FACSLyric™ flow cytometer.
5.6.3 BD CS&T beads
BD™ CS&T beads, in conjunction with BD FACSuite™ Clinical software, provide a standardized method for the quality control of optics, electronics, and for adjusting detector voltages and fluorescence compensation on the BD FACSLyric™ flow cytometer.
BD Multitest 6-color TBNK 5.6.4
BD Multitest™ 6-color TBNK with optional BD Trucount™ tubes is intended for use with BD FACSLyric™, BD FACSCanto™ II, and BD FACSCanto™ flow cytometers to determine the percentages and absolute counts of the following mature human lymphocyte subsets in peripheral whole blood for immunophenotyping:
- T lymphocytes (CD3+) ●
- . B lymphocytes (CD19*)
- Natural killer (NK) lymphocytes (CD3-CD16+ and/or CD56*)
- Helper/inducer T lymphocytes (CD3+CD4+)
- Suppressor/cytotoxic T lymphocytes (CD3CD8) ●
This reagent is indicated for use in the immunological assessment of normal individuals, and patients having, or suspected of having, immune deficiency.
BD Multitest IMK Kit 5.6.5
BD Multitest™ IMK kit with optional BD Trucount™ tubes is intended for use with BD FACSLyric™, BD FACSCanto™ II, BD FACSCanto™ , and BD FACSCalibur™ flow cytometers to determine the percentages and absolute counts of the following mature human lymphocyte subsets in peripheral whole blood for immunophenotyping:
- T lymphocytes (CD3+) .
- B lymphocytes (CD19+) ●
- Natural killer (NK) lymphocytes (CD3-CD16+ and/or CD56+)
- . Helper/inducer T lymphocytes (CD3+CD4+)
- Suppressor/cytotoxic T lymphocytes (CD3+CD8+) ●
This reagent is indicated for use in the immunological assessment of normal individuals, and patients having, or suspected of having, immune deficiency.
8
5.6.6 BD Multitest CD3/CD8/CD45/CD4
BD Multitest™ CD3/CD8/CD45/CD4 with optional BD Trucount™ tubes is intended for use with BD FACSLyric™, BD FACSCanto™ II, BD FACSCanto™, and BD FACSCalibur™ flow cytometers to determine the percentages and absolute counts of the following mature human lymphocyte subsets in peripheral whole blood for immunophenotyping:
- T lymphocytes (CD3+) ●
- . Helper/inducer T lymphocytes (CD3+CD4+)
- Suppressor/cvtotoxic T 1vmphocytes (CD3+CD8+) .
This reagent is indicated for use in the immunological assessment of normal individuals, and patients having, or suspected of having, immune deficiency.
BD Multitest CD3/CD16+CD56/CD45/CD19 5.6.7
BD Multitest™ CD3/CD16+CD56/CD45/CD19 with optional BD Trucount™ tubes is intended for use with BD FACSLyric™, BD FACSCanto™ II, BD FACSCanto™, and BD FACSCalibur™ flow cytometers to determine the percentages and absolute counts of the following mature human lymphocyte subsets in peripheral whole blood for immunophenotyping:
- · T lymphocytes (CD3+)
- Natural killer (NK) lymphocytes (CD3-CD16+ and/or CD56+) .
- B lymphocytes (CD3-CD19+) .
This reagent is indicated for use in the immunological assessment of normal individuals, and patients having, or suspected of having, immune deficiency.
5.6.8 BD Multi-Check Control
BD™ Multi-Check Control is intended as a complete process control for immunophenotyping by flow cytometry. It is a control for antibody staining, red blood cell (RBC) lysis, instrument setup and performance, and data analysis on BD FACSLyric™, BD FACSCanto™ II, BD FACSCanto™, and BD FACSCalibur™ flow cvtometers.
5.6.9 BD Multi-Check CD4 Low Control
BD™ Multi-Check CD4 Low Control is intended as a complete process control for immunophenotyping by flow cytometry. It is a control for antibody staining, red blood cell (RBC) lysis, instrument setup and performance, and data analysis on BD FACSLyric™, BD FACSCanto™ II, BD FACSCanto™, and BD FACSCalibur™ flow cytometers.
9
5.6.10 BD Trucount Tubes
BD Trucount™ tubes are intended for use with appropriated BD IVD reagent products on BD FACSLyric™, BD FACSVia™, BD FACSCanto™, BD FACSCanto™ II and BD FACSCalibur™ flow cytometers to determine absolute counts of leucocytes in erythrocyte-lysed whole blood.
5.6 Comparison of Technological Characteristics with the Predicate Device
A comparison of the similarities and differences between the subject device and the predicate device is presented in Table 5-1 to Table 5-4
10
| Table 5-1 Classification and Methodology | |||
|---|---|---|---|
| -- | ------------------------------------------ | -- | -- |
| Feature/Attribute | Subject Device | Predicate Device | |
|---|---|---|---|
| Device | |||
| Classification and | |||
| Product Code | Automated Differential Cell Counter Regulatory Class: II Regulation Number: 21 CFR 864.5220 Product Code: OYE | Same | |
| Assay | |||
| Methodology | Flow Cytometry | Same | |
| Detection/Assay | |||
| Principle | Immunofluorescence | Same | |
| Monoclonal | |||
| Antibody Reagents | Multitest 6-color TBNK Multitest IMK kit Multitest CD3/CD8/CD45/CD4 Multitest CD3/CD16 +CD56/CD45/CD19 All with optional Trucount tubes to provide identification and | ||
| enumeration of Total CD3+, CD3+CD4+, CD3+CD8+, | |||
| CD16+CD56+ and CD19+ percentages and absolute count | |||
| results | Same | ||
| Specimen Type | Peripheral whole blood | Same | |
| Sample Volume | 50 µL | Same | |
| Sample | |||
| Preparation | Manual | Manual Automated (when used with optional accessory FACS | |
| Sample Prep Assistant III ) | |||
| Feature/Attribute | Subject Device | Predicate Device | |
| Intended Use/ | Flow Cytometer | ||
| Indications for | |||
| Use - Flow | |||
| Cytometer | The BD FACSLyric flow cytometer is intended for use as an in | ||
| vitro diagnostic device for immunophenotyping using up to six | |||
| fluorescence detection channels and two light scatter channels | |||
| using a blue (488-nm) and a red (640-nm) laser. It is intended for | |||
| use with in vitro diagnostic (IVD) assays and software that are | |||
| indicated for use with the instrument. | |||
| BD Multitest 6-color TBNK, BD Multitest IMK kit, BD Multitest | |||
| CD3/CD8/CD45/CD4, and BD Multitest | |||
| CD3/CD16+CD56/CD45/CD19, all with optional BD Trucount | |||
| tubes, are intended for use on the BD FACSLyric flow cytometer | |||
| with peripheral whole blood for immunophenotyping. These | |||
| reagents are indicated for use in the immunological assessment of | |||
| normal individuals, and patients having, or suspected of having, | |||
| immune deficiency. These reagents determine the percentages | |||
| and absolute counts of the following mature human lymphocyte | |||
| subsets: | |||
| BD Multitest 6-color TBNK with optional BD Trucount tubes | |||
| T lymphocytes (CD3+) | |||
| ● | |||
| B lymphocytes (CD19+) | |||
| ● | |||
| Natural killer (NK) lymphocytes (CD3-CD16+ and/or | |||
| ● | |||
| CD56+) | |||
| Helper/inducer T lymphocytes (CD3+CD4+) | |||
| ● | |||
| Suppressor/cytotoxic T lymphocytes (CD3+CD8+) | |||
| ● | |||
| BD Multitest IMK kit with optional BD Trucount tubes | |||
| T lymphocytes (CD3+) | |||
| ● | The BD FACSCanto II flow cytometers (4-2-2 and 5-3 | ||
| configurations) function as part of a system with dedicated clinical | |||
| software intended for use with cleared or approved in vitro | |||
| diagnostic (IVD) assays that are indicated for use with the | |||
| instrument for the identification and enumeration of human cell | |||
| subsets. Only six detection channels using a blue (488 nm) and a | |||
| red (633 nm) laser have been cleared for in vitro diagnostic use. For | |||
| use with or without the BD FACS Sample Prep Assistant III. | |||
| The BD FACSCanto II flow cytometer (4-2 configuration) is | |||
| intended for use as an In Vitro Diagnostic device for identification | |||
| and enumeration of lymphocyte subsets in human cells in | |||
| suspension. | |||
| · Immunophenotyping in clinical laboratories, using previously | |||
| cleared in vitro diagnostic assays for flow cytometry. | |||
| · Identification and enumeration of lymphocyte subsets in human | |||
| cells in suspension. | |||
| · For in vitro diagnostic use. | |||
| · For use with or without the BD FACS Sample Prep Assistant III | |||
| See intended use for BD Multitest reagents in Table 5-4. | |||
| B lymphocytes (CD19+) | |||
| ● | |||
| Natural killer (NK) lymphocytes (CD3-CD16+ and/or | |||
| ● | |||
| CD56+) | |||
| Helper/inducer T lymphocytes (CD3+CD4+) | |||
| ● | |||
| Suppressor/cytotoxic T lymphocytes (CD3+CD8+) | |||
| ● | |||
| Feature/Attribute | Subject Device | Predicate Device | |
| BD Multitest CD3/CD8/CD45/CD4 with optional BD Trucount | |||
| tubes | |||
| • T lymphocytes (CD3+) | |||
| • Suppressor/cytotoxic T lymphocytes (CD3+CD8+) | |||
| • Helper/inducer T lymphocytes (CD3+CD4+) | |||
| BD Multitest CD3/CD16+CD56/CD45/CD19 with optional BD | |||
| Trucount tubes | |||
| • T lymphocytes (CD3+) | |||
| • Natural killer (NK) lymphocytes (CD3-CD16+ and/or CD56+) | |||
| • B lymphocytes (CD3-CD19+) | |||
| Maximum | |||
| Parameter | |||
| Detectors | IVD detection channels – Six Fluorescence channels plus forward scatter and side scatter | Same | |
| Forward Scatter | |||
| Detection | Photodiode with built-in 488/10 bandpass filter | Same | |
| Fluorescence and | |||
| Side Scatter | |||
| Detection | Side scatter and fluorescence | ||
| • Reflective optics with single transmission bandpass filter in front of each PMT | |||
| • High performance PMT modules for all fluorescence and side scatter channels | |||
| • Light collected by objective lens is delivered by fiber optics to specially designed detector arrays | |||
| • The cuvette flow cell is gel-coupled by refractive index-matching optical gel to the fluorescence objective lens (1.2 NA) for optimal collection efficiency. | Same | ||
| Forward and Side | |||
| Scatter Sensitivity | Enables separation of fixed platelets from noise. | Same | |
| Sample | |||
| Identification | Sample identification can be done through manual entry of sample information into the software or using an optional barcode reader. | Same | |
| Optical | |||
| Configurations | • 2-laser (blue, red), 4-color (3-1) | ||
| • 2-laser (blue, red), 6-color (4-2) | |||
| • 3-laser (blue, red, violet), 8-color (4-2-2) | • 2-laser (blue, red), 6-color (4-2) | ||
| • 2 laser (blue, red), 8-color (5-3) | |||
| • 3-laser (blue, red, violet), 8-color (4-2-2) | |||
| Feature/Attribute | Subject Device | Predicate Device | |
| 3-laser (blue, red, violet), 10-color (4-3-3) | |||
| Only up to six detection channels using red and blue lasers are | |||
| for IVD use. | Only up to six detection channels using red and blue | ||
| Lasers Used for | |||
| IVD Detection | |||
| Channels | Blue Wavelength: 488 nm Optical power: 20 mW Red Wavelength: 640 nm Optical power: 40 mW | Blue Wavelength: 488 nm Optical power: 20 mW Red Wavelength: 633 nm Optical power: 17 mW | |
| Electronics | Up to 35000 events/sec | Up to 10000 events/sec | |
| Sample | |||
| Introduction | Manual loading onto the tube port of the flow cytometer Automated loading through a multi-tube FACS Universal | ||
| Loader (hold one 30 or 40-tube rack) | Manual loading onto the tube port of the flow cytometer Automated loading through a multi-tube FACS Loader (carousel to | ||
| hold up to 40 tubes) | |||
| Software | FACSuite Clinical software with the following Multitest assay | ||
| modules: Multitest 6-Color Assays Multitest 4-Color Assays | FACSCanto Clinical software with Multitest 6-Color and Multitest | ||
| 4-Color assays included as panels within the software | |||
| Sample Analysis | Automated gating of cellular populations by the software and | ||
| manual adjustment by the user | Same | ||
| Results Reporting | Software- assisted report generation | Same | |
| Fluidics | Uses FACSFlow as the sheath fluid Uses 10% bleach solution for system cleaning System waste products are collected in the waste container | ||
| (5L standard size) Uses FACSFlow as the sheath fluid | Uses FACSFlow as the sheath fluid, together with FACS | ||
| shutdown solution and FACS cleaning solution System waste products are collected in the waste container (10 | |||
| L standard size) |
Table 5-2 Instrument and Software
11
12
13
14
| Feature/ Attribute | Subject Device | Predicate Device | |
|---|---|---|---|
| Quality Control and Setup Beads | |||
| Intended Use/ | |||
| Indications for Use | BD FC beads 7-color kit | ||
| The BD FC beads 7-color kit (BD FC beads), in conjunction | |||
| with BD FACSuite Clinical software and BD CS&T beads, are | |||
| used to establish fluorescence compensation for the BD | |||
| FACSLyric flow cytometer. |
BD CS&T beads
BD CS&T beads, in conjunction with BD FACSuite Clinical
software, provide a standardized method for the quality control
of optics, electronics, and fluidics, and for adjusting detector
voltages and fluorescence compensation on the BD FACSLyric
flow cytometer. | BD FACS 7-Color Setup Beads
For in vitro diagnostic use on a BD FACSCanto flow cytometer
with BD FACSCanto software. The beads are used to adjust
fluorescent detector voltages, to set fluorescence compensation, and
to monitor daily instrument performance. | |
| Quality Control &
Instrument Setup | Daily QC performed using CS&T beads QC is also preformed every 6 months using CS&T beads.
It includes all of the measurements performed in daily QC
along with additional more detailed measurements and an
automatic laser alignment. Daily instrument setup using CS&T beads FC Beads are run every 2 months to measure and reset
instrument spectral overlap values as part of the instrument
setup | Daily QC performed using FACS 7-color setup Daily instrument setup using FACS 7-color setup beads | |
15
| Table 5-4 Monoclonal Antibody Reagents and Process Controls | ||
|---|---|---|
| Feature/
| Attribute | Subject Device | Predicate Device | ||
|---|---|---|---|---|
| Multitest 6-Color TBNK | ||||
| Intended | ||||
| Use/ | ||||
| Indications | ||||
| for Use | BD Multitest 6-color TBNK with optional BD Trucount tubes is | |||
| intended for use with BD FACSLyric, BD FACSCanto II, and BD | ||||
| FACSCanto flow cytometers to determine the percentages and | ||||
| absolute counts of the following mature human lymphocyte subsets | ||||
| in peripheral whole blood for immunophenotyping: | ||||
| T lymphocytes (CD3+) B lymphocytes (CD19+) Natural killer (NK) lymphocytes (CD3-CD16+ and/or | ||||
| CD56+) Helper/inducer T lymphocytes (CD3+CD4+) Suppressor/cytotoxic T lymphocytes (CD3+CD8+) This reagent is indicated for use in the immunological assessment | ||||
| of normal individuals, and patients having, or suspected of having, | ||||
| immune deficiency. | BD Multitest 6-color TBNK reagent with optional BD Trucount | |||
| tubes is a six-color 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. | | |
| Feature/
Attribute | Subject Device | Predicate Device | | |
| | Multitest IMK Kit | | | |
| Intended
Use/
Indications
for Use | BD Multitest IMK kit with optional BD Trucount tubes is intended
for use with BD FACSLyric, BD FACSCanto II, BD FACSCanto ,
and BD FACSCalibur flow cytometers to determine the
percentages and absolute counts of the following mature human
lymphocyte subsets in peripheral whole blood for
immunophenotyping:
• T lymphocytes (CD3+)
• B lymphocytes (CD19+)
• Natural killer (NK) lymphocytes (CD3-CD16+ and/or
CD56+)
• Helper/inducer T lymphocytes (CD3+CD4+)
• Suppressor/cytotoxic T lymphocytes (CD3+CD8+)
This reagent is indicated for use in the immunological assessment
of normal individuals, and patients having, or suspected of having,
immune deficiency. | Intended Use
MultiTESTCD3/CD16+56/CD45/CD19 reagent is a four-color
reagent for identifying and enumerating percentages and absolute
counts of T (CD3+), NK (natural killer) (CD3- CD16+CD56+), and
B (CD3-CD19 +) lymphocyte subsets by direct
immunofluorescence. The MultiTEST IMK contains the same
MultiTEST CD3/CD16+CD56/CD45/CD19) reagent, MultiTEST
CD3/CD8/CD45/CD4 reagent, and MultiTEST IMK Kit Lysing
Solution. Helper/inducer T (CD3+CD4+) and suppressor/cytotoxic T
(CD3+CD8+) lymphocyte subset percentages and absolute counts
can be obtained from the MultiTEST CD3/CD8/CD45/CD4 reagent
included in the kit. Subsets of lymphocytes are useful in managing
some forms of immunodeficiency diseases.
Indications for Use
• For use with Becton Dickinson FACS flow cytometers equipped
with a blue (488-nm) and red diode (635-nm) laser.
• Monoclonal antibody reagents for identification and
enumeration of mature human lymphocyte subsets in peripheral
blood of normal individuals and patients with certain immune
dysfunction.
• MultiTEST CD3/CD16+56/CD45/CD19 provides percentages
and absolute counts of T (CD3+), NK (CD3-CD16+CD56+) and
B (CD3-CD19+) lymphocytes. MultiTEST
CD3/CD8/CD45/CD4 provides percentages and absolute counts
of T (CD3+), helper/inducer T (CD3+CD4+) and
suppressor/cytotoxic T (CD3+CD8+) lymphocytes.
• For use with erythrocyte lysed whole blood without an isotype
control.
• To characterize and monitor forms of auto immune diseases,
such as lupus.
• To characterize and monitor congenital or acquired
immunodeficiences, such as SCID or AIDS.
For in vitro diagnostic use. | | |
| Feature/
Attribute | Subject Device | Predicate Device | | |
| | Multitest CD3/CD8/CD45/CD4 | | | |
| Intended
Use/
Indications
for Use | BD Multitest CD3/CD8/CD45/CD4 with optional BD Trucount
tubes is intended for use with BD FACSLyric, BD FACSCanto II,
BD FACSCanto, and BD FACSCalibur flow cytometers to
determine the percentages and absolute counts of the following
mature human lymphocyte subsets in peripheral whole blood for
immunophenotyping:
T lymphocytes (CD3+)
●
Helper/inducer T lymphocytes (CD3+CD4+)
●
Suppressor/cytotoxic T lymphocytes (CD3CD8)
●
This reagent is indicated for use in the immunological assessment
of normal individuals, and patients having, or suspected of having,
immune deficiency. | Intended Use
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/cytotoxic T Lymphocyte
subsets by direct immunofluorescence. Subsets of T Lymphocytes
are useful in managing immunodeficiency diseases. To characterize
and monitor congenital or acquired immunodeficiences, such as
SCID or AIDS.
Indications for Use
For the FACS family of flow cytometers equipped with a blue
●
(488-nm) and a red diode (635-nm) laser.
A monoclonal antibody reagent for identification and
●
enumeration of mature human T lymphocyte subsets in human
peripheral blood.
For use with erythrocyte lysed whole blood.
●
To characterize and monitor forms of autoimmune diseases,
●
such as lupus.
To characterize and monitor congenital or acquired
●
immunodeficiences, such as SCID or AIDS. | | |
| | For in vitro diagnostic use.
Multitest CD3/CD16+CD56/CD45/CD19 | | | |
| Intended
Use/
Indications
for Use -
Multitest
Reagents | BD Multitest CD3/CD16+CD56/CD45/CD19 with optional BD
Trucount tubes is intended for use with BD FACSLyric, BD
FACSCanto II, BD FACSCanto, and BD FACSCalibur flow
cytometers to determine the percentages and absolute counts of the
following mature human lymphocyte subsets in peripheral whole
blood for immunophenotyping:
T lymphocytes (CD3+)
●
Natural killer (NK) lymphocytes (CD3-CD16+ and/or
●
CD56+)
B lymphocytes (CD3-CD19+)
● | Intended Use
MultiTESTCD3/CD16+56/CD45/CD19 reagent is a four-color
reagent for identifying and enumerating percentages and absolute
counts of T (CD3+), NK (natural killer) (CD3- CD16+CD56+), and
B (CD3-CD19 +) lymphocyte subsets by direct
immunofluorescence. The MultiTEST IMK contains the same
MultiTEST CD3/CD16+CD56/CD45/CD19) reagent, MultiTEST
CD3/CD8/CD45/CD4 reagent, and MultiTEST IMK Kit Lysing
Solution. Helper/inducer T (CD3+CD4+) and suppresser/cytotoxic T
(CD3+CD8+) lymphocyte subset percentages and absolute counts
can be obtained from the MultiTEST CD3/CD8/CD45/CD4 reagent | | |
16
17
18
| Feature/
| Attribute | Subject Device | Predicate Device |
|---|---|---|
| This reagent is indicated for use in the immunological assessment | ||
| of normal individuals, and patients having, or suspected of having, | ||
| immune deficiency. | included in the kit. Subsets of lymphocytes are useful in managing | |
| some forms of immunodeficiency diseases. |
Indications for Use
For use with Becton Dickinson FAC flow cytometers equipped
with a blue (488-nm) and red diode (635-nm) laser. Monoclonal antibody reagents for identification and
enumeration of mature human lymphocyte subsets in peripheral
blood of normal individuals and patients with certain immune
dysfunction. MultiTEST CD3/CD16+56/CD45/CD19 provides percentages
and absolute counts of T (CD3+), NK (CD3-CD16+CD56) and
B (CD3-CD19+) lymphocytes. |
| Trucount Tubes | | |
| Intended
Use/
Indications
for Use | BD Trucount tubes are intended for use with appropriated BD IVD
reagent products on BD FACSLyric, BD FACSVia, BD
FACSCanto II, BD FACSCanto and BD FACSCalibur flow
cytometers to determine absolute counts of leucocytes in
erythrocyte-lysed whole blood. | Intended Use
TruCount Absolute Count Tubes are intended for use as an accessory
to TriTEST in vitro diagnostics, such as that described in K965053
(CD3/CD4/CD45), to allow computation of positive cells per know
volume of blood, using flow cytometry.
Indications for Use
For use with FACS Loader For use with in vitro diagnostic immunophenotyping
reagents For use in erythrocyte lysed whole blood For use to obtain absolute counts by flow cytometry |
| Multi-Check Controls | | |
| Feature/
Attribute | Subject Device | Predicate Device |
| Intended Use/
Indications for Use | BD Multi-Check Control is intended as a complete process control
for immunophenotyping by flow cytometry. It is a control for
antibody staining, red blood cell (RBC) lysis, instrument setup and
performance, and data analysis on BD FACSLyric, BD
FACSCanto II, BD FACSCanto, and BD FACSCalibur flow
cytometers. | Whole Blood Flow Control (WBFC) is a stabilized preparation of
human peripheral leukocytes and erythrocytes to be used as a control
in the complete immunophenotyping process which includes:
antibody staining, RBC lysis, instrument set-up and instrument
performance. |
| Multi-Check CD4 Low Control | | |
| | BD Multi-Check CD4 Low Control is intended as a complete
process control for immunophenotyping by flow cytometry. It is a
control for antibody staining, red blood cell (RBC) lysis, instrument
setup and performance, and data analysis on BD FACSLyric, BD
FACSCanto II, BD FACSCanto, and BD FACSCalibur flow
cytometers. | StatusFlowLo is intended as a complete process control for
immunophenotyping by flow cytometry. It is a control for antibody
staining, RBC lysis, instrument set-up, instrument performance and
data analysis. |
19
20
A summary of the comparison is included as follows:
The subject device is similar to the predicate device as follows:
- Used for identification and enumeration of human lymphocyte cell subsets ●
- Performs the same flow cytometric assays with the same Multitest reagents and the same process controls .
- Uses the same Trucount Tubes with a known number of beads per sample volume to calculate absolute cell counts .
- Based on multicolor fluorescence ●
- Uses red, blue and violet lasers to provide excitation illumination for the specific wavelengths of the fluorophores, only the . red and blue are used in the Multitest assays.
- Uses dichroic mirrors to split fluorescence emissions into wavelength ranges for each fluorophore to be detected .
- Uses photomultiplier tubes (PMTs) for the detection of fluorescence emission signal .
The subject device differs from the predicate device as follows:
- Is available in four optical configurations: 3-1, 4-2, 4-2-2, and 4-3-3, whereas the Predicate in 3 optical . configurations: 4-2, 4-2-2 and 5-3.
- Has a high powered red laser that yields higher detection sensitivity compared to the predicate device .
- Instrument OC is performed using CS&T Beads and fluorescence compensation is established by using FC beads 7-color . kit. whereas for the predicate device. FACS 7-color setup beads are used to adjust fluorescent detector voltages, to set fluorescence compensation, and to monitor daily instrument performance. The subject device measures more parameters and is capable of more accurately assessing the instrument performance.
- . Uses the optional FACS Universal Loading tubes in 30- or 40-tube rack, whereas the predicate device uses FACS Loader which accommodates up to 40 tubes in a carousel.
- Smaller footprint with no separate wet for fluidics and generates much lower noise output than the predicate device. .
21
5.7 Performance Data
The following bench (Table 5-5) and clinical (Table 5-6) performance data were provided to support the substantial equivalency determination.
| Studv | Standard/Reference | Objective | Results |
|---|---|---|---|
| Intra-instrument | |||
| Optical | |||
| Configuration | |||
| Equivalency | N/A | To demonstrate system level performance | |
| equivalency across the 3-1 (4-color), 4-2 (6- | |||
| color), 4-2-2 (8-color), and 4-3-3 (10-color) | |||
| optical configurations of the FACSLyric flow | |||
| cytometer as measured by QC and setup | |||
| performance parameters generated utilizing | |||
| CS&T beads and FC beads. | System level optical equivalency was | ||
| demonstrated between the four configurations | |||
| (3-1, 4-2, 4-2-2 and 4-3-3) of the FACSLyric | |||
| system. | |||
| Inter-instrument | |||
| Optical | |||
| Configuration | |||
| Equivalency | CLSI EP09-A3, | ||
| Measurement Procedure | |||
| Comparison and Bias | |||
| Estimation Using Patient | |||
| Samples: Approved | |||
| Guideline- Third Edition | To demonstrate performance equivalency | ||
| between the 3-1 (4-color), 4-2 (6-color), 4-2-2 | |||
| (8-color), and 4-3-3 (10-color) optical | |||
| configurations of the FACSLyric flow | |||
| cytometer through testing multiple instruments | |||
| of different configurations (inter-instrument) | |||
| using patient and normal donor samples | |||
| stained with Multitest IMK kit and Multitest | |||
| 6-Color TBNK in Trucount tubes. | The performance equivalency of the 6 IVD | ||
| channels between the 3-1, 4-2, 4-2-2 and 4-3-3 | |||
| optical configurations of the FACSLyric flow | |||
| cytometer have been demonstrated. | |||
| Study | Standard/Reference | Objective | Results |
| Method | |||
| Comparison | CLSI EP09-A3, | ||
| Measurement Procedure | |||
| Comparison and Bias | |||
| Estimation Using Patient | |||
| Samples; Approved | |||
| Guideline- Third Edition | To determine the method bias between the | ||
| ● | |||
| FACSLyric system with Multitest | |||
| reagents and the FACSCanto II system | |||
| with Multitest reagents on the | |||
| determination of CD3+, CD3+CD4+, | |||
| CD3+CD8+, CD19+ and CD16+56+ | |||
| percentage and absolute counts. | |||
| To demonstrate equivalency between | |||
| ● | |||
| FACSLyric Universal Loader (UL) | |||
| acquisition and FACSLyric manual | |||
| acquisition when using the Multitest IMK | |||
| kit and Multitest 6-Color TBNK with | |||
| Trucount tubes in the determination of | |||
| CD3+, CD3+CD4+, CD3+CD8+, CD19+ | |||
| and CD16+56+ percentage and absolute | |||
| counts. | The method bias between the FACSLyric and | ||
| the FACSCanto II, in the determination of | |||
| CD3+, CD3+CD4+, CD3+CD8+, CD19+ and | |||
| CD16+56+ percentage and absolute counts. | |||
| met the acceptance criteria using the Multitest | |||
| IMK kit and Multitest 6-Color TBNK with | |||
| Trucount tubes. In addition, equivalency | |||
| between the FACSLyric UL acquisition and | |||
| Manual acquisition was demonstrated. | |||
| Within-site | |||
| Precision | CLSI EP05-A3, Evaluation | ||
| of Precision of Quantitative | |||
| Measurement Procedures: | |||
| Approved Guideline-Third | |||
| Edition. | To evaluate the within-site precision | ||
| performance of FACSLyric system using the | |||
| Multitest IMK kit and Multitest 6-Color | |||
| TBNK with Trucount tubes. | All acceptance criteria were met. The within- | ||
| site precision performance of FACSLyric | |||
| system using the Multitest IMK kit and | |||
| Multitest 6-Color TBNK with Trucount tubes | |||
| satisfied the within-run and total precision | |||
| performance requirements. | |||
| Whole Blood | |||
| Repeatability | CLSI EP05-A3, Evaluation | ||
| of Precision of Quantitative | |||
| Measurement Procedures; | |||
| Approved Guideline-Third | |||
| Edition. | To verify repeatability performance across all | ||
| the FACSLyric instruments of different | |||
| configurations, using whole blood from patient | |||
| and normal donor samples, stained with the | |||
| Multitest IMK kit and Multitest 6-Color | |||
| TBNK with Trucount tubes. | Repeatability performance was demonstrated | ||
| across all the instruments with different | |||
| configurations. All lymphocyte subsets | |||
| met %CV and SD acceptance criteria. | |||
| Linearity | CLSI EP6-A, Evaluation of | ||
| the Linearity of Quantitative | |||
| Measurement Procedures: A | |||
| Statistical Approach: | |||
| Approved Guideline. | To evaluate the linear range of the FACSLyric | ||
| system using the Multitest IMK kit and | |||
| Multitest 6-Color TBNK with Trucount tubes. | Acceptable linear ranges have been | ||
| established for each lymphocyte subset for | |||
| each of the Multitest reagents on FACSLyric | |||
| svstem. | |||
| Study | Standard/Reference | Objective | Results |
| Sample Carryover | CLSI H26-A2, Validation, | ||
| Verification, and Quality | |||
| Assurance of Automated | |||
| Hematology Analyzers; | |||
| Approved Standard- Second | |||
| Edition | To determine the percent sample carryover | ||
| based on acquisition of three highly | |||
| concentrated samples immediately followed | |||
| by acquisition of three low concentrated | |||
| samples on FACSLyric system. | All the results met the acceptance criteria of | ||
| system carryover less than or equal to 0.1% | |||
| for low carryover and less than or equal to | |||
| 0.5% for standard carryover on all three | |||
| FACSLyric instruments. To meet the low | |||
| carryover requirement the results | |||
| demonstrated that only a single SIT flush was | |||
| required. | |||
| Reagent Carryover | CLSI H26-A2 Validation, | ||
| Verification, and Quality | |||
| Assurance of Automated | |||
| Hematology Analyzers; | |||
| Approved Standard- Second | |||
| Edition. | To verify the capability of the FACSLyric | ||
| system to acquire samples with minimal | |||
| reagent carryover. | Results met the acceptance criteria were met. | ||
| The amount of reagent being carried over is | |||
| found to be well below the amount of reagent | |||
| required for effective staining of the sample. | |||
| Detection | |||
| Capability of LoB | |||
| and LoD | CLSI EP17-A2, Evaluation | ||
| of Detection Capability for | |||
| Clinical Laboratory | |||
| Measurement Procedures; | |||
| Approved Guideline-Second | |||
| Edition. | To evaluate the limit of blank (LoB) and limit | ||
| of detection (LoD) of the FACSLyric system | |||
| with Multitest IMK kit and Multitest 6-Color | |||
| TBNK with Trucount tubes. | The detection capability parameters for the | ||
| limit of blank (LoB) and limit of detection | |||
| (LoD) of the FACSLyric system were | |||
| established for BD Multitest reagents. For | |||
| CD4 lymphocyte subset absolute counts of | |||
| each of the reagents, the established LoB and | |||
| LoD were less than 50 cells/µL. | |||
| Detection | |||
| Capability of LoQ | CLSI EP17-A2, Evaluation | ||
| of Detection Capability for | |||
| Clinical Laboratory | |||
| Measurement Procedures; | |||
| Approved Guideline-Second | |||
| Edition. | To evaluate the limit of quantitation (LoQ) of | ||
| the FACSLyric system using Multitest IMK | |||
| kit and Multitest 6-Color TBNK, both with | |||
| Trucount tubes. | The LoQ of the FACSLyric system with | ||
| Multitest reagents was established for the | |||
| CD3+, CD3+CD4+, CD3+CD8+, CD19+, | |||
| CD16+CD56+ and CD45+ lymphocyte | |||
| subsets. The acceptance criteria were met and | |||
| the LOQ is less than 50 cells/µL for CD4 | |||
| lymphocyte subset absolute counts. | |||
| Setup and QC | |||
| Performance | N/A | To verify that Setup & QC Performance of the | |
| FACSLyric system meets the pre-defined | |||
| specifications. | All the Setup & QC performance results of the | ||
| FACSLyric system met the acceptance criteria | |||
| Study | Standard/Reference | Objective | Results |
| Setup and QC Stability | N/A | To verify the stability of system level Setup & QC on the FACSLyric system. | All the system level Setup & QC stability performance results on the FACSLyric system met the pre-defined specifications. |
| Study | Standard/Reference | Testing Approach | Results |
| Method | |||
| Comparison | CLSI EP09-A3, | ||
| Measurement Procedure | |||
| Comparison and Bias | |||
| Estimation Using Patient | |||
| Samples; Approved | |||
| Guideline- Third Edition | To evaluate performance equivalence of the | ||
| FACSLyric system and the FACSCanto II | |||
| system on the determination of lymphocyte | |||
| subsets using the Multitest 6-Color TBNK and | |||
| Multitest IMK kit, both with Trucount tubes, | |||
| using remnant, de-linked patient specimens. | A total of 332 specimens were enrolled for | ||
| testing with Multitest 6-Color TBNK (297 | |||
| evaluable), and 368 specimens were enrolled for | |||
| Multitest IMK kit (336 evaluable) at 5 clinical | |||
| sites. The acceptance criteria for all lymphocyte | |||
| subsets were met for the FACSLyric system. | |||
| The differences of the results between all the | |||
| specimens and the non-manipulated specimens | |||
| were very minimal, and no bias trend was | |||
| observed. Additional analysis per site and by | |||
| different EDTA anticoagulant formulations | |||
| (EDTA-K2 vs EDTA-K3) in the blood | |||
| collection tubes also showed minimal difference | |||
| with no trend observed. | |||
| Inter-laboratory | |||
| Reproducibility | CLSI EP05-A3, | ||
| Evaluation of Precision of | |||
| Quantitative Measurement | |||
| Procedures; Approved | |||
| Guideline-Third Edition. | To evaluate inter-laboratory reproducibility for | ||
| the FACSLyric system on the determination of | |||
| lymphocyte subsets using the Multitest 6- | |||
| Color TBNK and Multitest IMK kit in | |||
| Trucount tubes with a single lot of Streck CD- | |||
| Chex Plus process control material. | Inter-laboratory reproducibility was carried out | ||
| at four clinical sites. The variability for within | |||
| run, between run, between day, between site and | |||
| total precision per reagent and lymphocyte | |||
| subset was evaluated. The 97.5% one-sided | |||
| confidence interval (CI) on the within run and | |||
| total precision was estimated and compared to |
|
| Reference Intervals | CLSI EP28-A3c How to
Define and Determine
Reference Intervals in the
Clinical Laboratory,
Approved Guideline-
Second Edition. | To re-establish the reference intervals of a
normal male and female adult cohort, free of
hematological abnormality, using the
FACSLyric system for the Multitest 6-Color
TBNK and Multitest IMK kit, both with
Trucount tubes, on determination of
lymphocyte subsets using prospectively
procured and de-linked donor specimens at
one study site. | A total of 136 subjects were enrolled (134
evaluable for Multitest 6-Color TBNK and 130
evaluable for Multitest IMK kit) from one
clinical site. Reference Intervals for all
lymphocyte subsets in the Multitest 6-Color
TBNK and Multitest IMK kit were established
for the FACSLyric system. Differences were
observed between genders, but these differences
are not clinically significant. |
| Study | Standard/Reference | Testing Approach | Results |
| Specimen Stability | N/A | To generate data to support stability of venous
whole blood with EDTA anticoagulant when
testing the Multitest 6-Color TBNK and
Multitest IMK kit, both with Trucount tubes,
on the FACSLyric system using prospectively
procured and de-linked patient specimens
from at least two study sites. | A total of 227 specimens were enrolled for each
of the reagents from the two clinical sites. 180
specimens were evaluable for Multitest 6-Color
TBNK and 186 were evaluable for Multitest
IMK kit. The results from the study support the
claim of up to 24 hours Age of Blood and 6
hours Age of Stain for Multitest 6-Color TBNK.
and up to 48 hours Age of Blood and 24 hours
Age of Stain for Multitest IMK kit (include
Multitest CD3/CD8/CD45/CD4 and Multitest
CD3/CD16+CD56/CD45/CD19) on FACSLyric
system. |
Table 5-5 Bench Performance Summary
22
23
24
25
Table 5-6 Clinical Performance Summary
26
5.8 Conclusion
The FACSLyric flow cytometer demonstrates substantial equivalency to the FACSCanto II system with Multitest reagents.