(265 days)
BD FACSPresto System:
The BD FACSPresto System is an automated multicolor fluorescent imaging cytometer and absorbance spectrometer to be used in conjunction with single use reagent cartridges in performing the direct cell enumeration and measurement of absorbance spectrums.
· For use with the BD FACSPresto™ CD4/Hb Cartridge and BD FACSPresto™ CD4/Hb Cartridge Kit in the direct quantification and enumeration of CD4 absolute count, CD4 percentage of lymphocytes, and determination of hemoglobin concentration in normal and HIV positive patients, in conjunction with other laboratory and clinical findings.
· For use in children, adolescents, and adults.
· For use with human whole blood from fingerstick and/or venous collections in K2 EDTA blood collection tubes.
· Not for point-of-care use.
· For in vitro diagnostic use.
BD FACSPresto CD4/Hb Cartridge & BD FACSPresto CD4/Hb Cartridge Kit:
The BD FACSPresto CD4/Hb Cartridge is a single use reagent cartridge to be used with the BD FACSPresto™ System for performing the direct quantification and enumeration of CD4 absolute count, CD4 percentage of lymphocytes, and determination of hemoglobin concentration in normal and HIV positive patients, in conjunction with other laboratory and clinical findings.
· For use in children, adolescents, and adults
· For use with human whole blood from fingerstick and/or venous collections in K2 EDTA blood collection tubes.
· Not for point-of-care use.
· For in vitro diagnostic use.
BD Multi-Check Control:
The 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.
The BDTM Multi-Check control is also intended as a CD4 and %CD4 process control for antibody staining, instrument performance, and data analysis on the BD FACSPresto™ system, an imaging cytometer.
BD Multi-Check CD4 Low Control:
The 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 data analysis.
The BD™ Multi-Check CD4 low control is also intended as a CD4 and %CD4 process control for antibody staining, instrument performance, and data analysis on the BD FACSPresto™ system, an imaging cytometer.
Eurotrol FACSPresto Hb Control:
Eurotrol FACSPresto Hb Control is an assayed hemoglobin control intended for in vitro diagnostic use in the verification of the precision and accuracy of the BD FACSPrestoTM System.
The BD FACSPresto System is an accurate, robust, and portable CD4, %CD4, and hemoglobin (Hb) System. The BD FACSPresto System has fluorescence microscopy and light absorbance capabilities. In addition, the instrument has integrated BD FACSPresto Software and instrument quality controls.
The BD FACSPresto CD4/Hb Cartridge contains antibody-fluorophore conjugates dried on a reagent disc and is embedded with reagent quality controls. The cartridge is designed with onboard reagents that mix well into the blood sample, and enumerate cells populations using fluorescence only. The cartridge is designed with fluidic properties that distribute a sufficient volume and sample into the imaging field of view for precise cell counting.
The BD FACSPresto CD4 and %CD4 assays are designed to stain cells with antibody-fluorophore conjugates for three color fluorescence reading using the BD FACSPresto System. CD4 PE-Cy5 stains CD4-positive cells; while CD3-APC and CD45RA-APC stains total lymphocytes for use in the %CD4 calculation (CD3 stains T cells, while CD45RA stains B and NK cells in a patented formulation). CD14-PE is used for staining monocytes to exclude CD4 and/or CD45RA expressing monocytes from analysis.
BD Multi-Check Control and BD Multi-Check CD4 Low Control are process controls for the CD4 and %CD4 assay on the BD FACSPresto system. They are composed of human leukocytes and erythrocytes in a stabilizing medium and are intended to be used as a complete process control for antibody staining. instrument performance, and data analysis on the BD FACSPresto system.
The BD FACSPresto Hb assay is performed by a spectrophotometric method. using absorbance at an isobestic point for multiple forms of hemoglobin, with correction for scatter. The cartridge microfluidic channel permits absorbance reading of blood and of a reference area.
Eurotrol FACSPresto Hb Control is used as a process control for the Hb assay on the BD FACSPresto system. It is composed of purified bovine hemolysate and is intended to be used as an assayed hemoglobin process control intended for in vitro diagnostic use in the verification of the precision and accuracy of the BD FACSPresto System.
Here is a summary of the acceptance criteria and the study that proves the device meets them, based on the provided text:
Acceptance Criteria and Device Performance for BD FACSPresto System
1. Table of Acceptance Criteria and Reported Device Performance
The acceptance criteria are generally described as meeting CLSI document standards and "study acceptance criteria" or "acceptable results." Specific quantitative targets are less frequently provided in this summary but are indicated as having been met.
| Performance Characteristic | Acceptance Criteria (Implicit from "Standard" or "Results") | Reported Device Performance |
|---|---|---|
| Method Comparison (CD4 & %CD4) | Substantially equivalent to predicate system (BD FACSCalibur). | BD FACSPresto provided CD4 and %CD4 results that are substantially equivalent to the predicate system. |
| Method Comparison (Hb) | Substantially equivalent to reference system (Sysmex KX-21N). | BD FACSPresto provided Hb results that are substantially equivalent to the reference system. |
| Precision (BD FACSPresto - Bench) | Acceptable CV and/or SD results for within-run and total precision. | Acceptable CV and/or SD results reported for within-run and total precision for CD4, %CD4, and Hb using controls. |
| Linearity (BD FACSPresto - Bench) | Acceptable linearity for CD4, Lymphocyte, and Hb ranges. | Acceptable linearity demonstrated: CD4 (42-4872 cells/µL), Lymphocyte (124-10,713 cells/µL), Hb (2-26 g/dL). |
| Hemoglobin Assay Traceability | Hb assay traceable to HiCN method, linear and accurate (2-20 g/dL). | Hb assay is traceable to the HiCN method and is linear and accurate across the reported linear range (2-20 g/dL). |
| Analytical Sensitivity (CD4 LoD/LoQ) | LoD below claimed range; LoQ established. | LoD: 22 cells/uL, LoQ: 35 cells/uL (LoD below system's claimed range). |
| Analytical Sensitivity (Hb LoD/LoQ) | LoQ supports claimed range of 2-20 g/dL. | LoD: 0.91 g/dL, LoQ: 2 g/dL (supports claimed range). |
| Interference | No clinically significant interference; bias < 15% for CD4, %CD4, Hb. | No clinically significant interference for 33 of 34 analytes; one (Gamma Globulin) showed interference at max concentration but not mid/low. Bias < 15% for CD4, %CD4, Hb for all analytes. |
| Specimen Stability (Age of Blood / Stain) | Acceptance criteria met for all parameters; 1 hour stain for venous/capillary, 22-hour age for venous blood. | Acceptance criteria met. Supports 1 hour stain (venous & capillary) and 22-hour age of blood (venous). |
| Biocompatibility (Cytotoxicity) | Test article passed (no reactivity observed). | Test article passed (no reactivity) in 48-hour titration cytotoxicity / elution test. |
| Biocompatibility (Hypersensitivity) | Stimulation Index < 3 compared to negative control. | Stimulation Index < 3; considered non-sensitizer in mice. |
| Biocompatibility (Irritation) | PII score of 0. | PII score of 0; considered negligible irritant in rabbits. |
| EMC | Complies with IEC 61326-1:2012, IEC61326-2-6:2012, IEC 61000-3-2:2005, IEC 61000-3-3:2008. | System complies with listed IEC standards. |
| Electrical Safety | Complies with UL 61010-1:2004, IEC 61010-2-081:2002, IEC 61010-2-101:2009. | System complies with listed standards. |
| BD Multi-Check Controls - Value Assignment Verification | All data points fell within FACSPresto-assigned ranges. | All data points from 3 lots of controls, 3 instruments, 3 cartridge lots, and 18 min/2 hr incubation fell within ranges. |
| BD Multi-Check Controls - Precision | Acceptable SD and/or CV for within-run, between-run, and total precision; upper 97.5% CI passes acceptance criteria. | Acceptable SD and/or CV reported; all results passed acceptance criteria with upper 97.5% CI. |
| Eurotrol FACSPresto Hb Control - Value Assignment Verification | All data points fell within FACSPresto-assigned ranges. | All data points from 3 lots of each of 3 levels (N=9 each), at 3 clinical sites, fell within ranges. |
| Eurotrol FACSPresto Hb Control - Precision | Acceptable CV for within-run, between-run, and total precision. | Acceptable CV results reported for within-run, between-run, and total precision across multiple stain times and lots. |
| Clinical Method Comparison | Acceptance criteria for CD4, %CD4, and Hb in venous and capillary whole blood successfully met for all sites. | Acceptance criteria met for CD4, %CD4, and Hb in venous (N=796) and capillary (N=692) samples across 8 clinical sites. |
| Clinical Precision | All precision requirements (repeatability, reproducibility, site-to-site) met for CD4, %CD4, and Hb. | Acceptance criteria met for precision repeatability, reproducibility, and site-to-site reproducibility. |
| Clinical Linearity | Acceptance criteria met for CD4, Lymphocytes, and Hb, supporting product claims. | Acceptance criteria met; results support linearity product claims. |
| Clinical Sample Stability | Acceptance criteria met; supports 1 hour staining (capillary/venous) and up to 22 hours venous blood storage. | Acceptance criteria met; results support product claims. |
| Reference Intervals | Established for CD4, %CD4, and Hb in a normal reference cohort. | Final reference ranges established for CD4, %CD4, and Hb, partitioned by parameter and gender. |
| BD Multi-Check Control Validation (Clinical) | At least 95% of data points fell within FACSPresto-assigned ranges. | At least 95% of data points fell within FACSPresto-assigned ranges during validation at 3 clinical sites over 20+ days using multiple lots/instruments/reagents. |
| Eurotrol FACSPresto Hb Control Validation (Clinical) | All data points fell within FACSPresto-assigned ranges. | All data points fell within FACSPresto-assigned ranges during validation at 3 clinical sites over 10 days using multiple lots/instruments/cartridges. |
2. Sample Size and Data Provenance
- Test Set Sample Sizes:
- Bench Method Comparison: VP, N = 107 (CD4 & %CD4); FS, N = 84 (CD4 & %CD4); VP, N = 84 (Hb); FS, N = 108 (Hb)
- Bench Precision: Streck CD-Chex Plus (Normal and CD4-Low) N = 168; Eurotrol FACSPresto Hb Controls (Levels 1-3) N = 252.
- Bench Linearity: N = 33 for each parameter (CD4, Lymphocyte, Hb).
- Hemoglobin Assay Traceability: N = 4-20 depending on bin.
- Analytical Sensitivity (CD4): LoD N = 60, LoQ N = 180.
- Analytical Sensitivity (Hb): LoD N = 300, LoQ N = 60.
- Clinical Method Comparison: N = 796 venous, N = 692 capillary (normal and HIV infected subjects).
- Clinical Linearity: Number of prospectively procured specimens not explicitly stated, but "low and high concentration pools were created from a specimen".
- Clinical Sample Stability: Number of samples not explicitly stated.
- Reference Intervals: Number of adults in "normal reference cohort" not explicitly stated.
- Data Provenance:
- The text indicates that clinical studies involved "De-identified and delinked prospectively enrolled normal and HIV infected subjects from 8 clinical sites" for method comparison and prospectively procured specimens for clinical linearity.
- Bench studies were likely conducted in-house.
- Country of origin is not explicitly stated, but the submission is to the U.S. FDA by BD Biosciences, a U.S.-based company, suggesting U.S. or international data accepted by U.S. regulatory bodies. The reference to "Clinical Validation data was collected at 3 clinical trial sites" (for controls) also implies clinical settings.
3. Number of Experts and Qualifications for Ground Truth
The document does not specify the number of experts or their qualifications used to establish ground truth for the test set.
4. Adjudication Method
The document does not specify any adjudication method (e.g., 2+1, 3+1, none) for the test set.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
A MRMC comparative effectiveness study was not conducted as described for AI vs. human readers. This device is an automated diagnostic system for laboratory parameters, not an interpretation aid for human readers.
6. Standalone Performance
Yes, standalone performance was done. The entire summary describes the performance of the BD FACSPresto System (algorithm only without human-in-the-loop for result generation) in directly quantifying CD4 absolute count, CD4 percentage of lymphocytes, and hemoglobin concentration. The system is an "automated multicolor fluorescent imaging cytometer and absorbance spectrometer."
7. Type of Ground Truth Used
The ground truth used was based on:
- Comparison to predicate and reference devices:
- For CD4 and %CD4: BD FACSCalibur using BD Tritest CD3/CD4/CD45 with BD Trucount Tubes (flow cytometry, a recognized standard).
- For Hb: Sysmex Automated Hematology Analyzer KX-21N (automated hematology analyzer using absorbance spectrophotometry, a recognized standard) and the HiCN method for hemoglobin determination (a recognized reference method).
- CLSI (Clinical and Laboratory Standards Institute) guidelines: Many performance characteristics (precision, linearity, analytical sensitivity, interference, specimen stability, reference intervals) were evaluated against CLSI standards, implying that these standards define the acceptable "ground truth" or clinical validity for such measurements.
8. Sample Size for Training Set
The document does not explicitly state the sample size used for a "training set." This device is a diagnostic instrument system, not a machine learning algorithm in the typical sense that would have a distinct training phase with a dedicated dataset described in this way. The development and calibration would typically involve extensive internal data, but the summary focuses on verification and validation studies.
9. How the Ground Truth for the Training Set Was Established
As no specific "training set" is described for algorithm training in the context of typical machine learning, no method for establishing ground truth for such a set is provided. The development of the instrument's algorithms and parameters would have relied on established laboratory methods and scientific principles for cell counting and hemoglobin measurement, likely validated against gold standard instruments and methods during product development.
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Image /page/0/Picture/1 description: The image shows the logo for the U.S. Department of Health and 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 caduceus is rendered in black, and the text is also in black.
Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002
December 17, 2015
BECTON, DICKINSON AND COMPANY CATHERINE BESSETTE, PHD SR. REGULATORY AFFAIRS SPECIALIST 2350 QUME DRIVE SAN JOSE CA 95131
Re: K150815
Trade/Device Name: BD FACSPresto System
BD FACSPresto CD4/Hb Cartridge BD FACSPresto CD4/Hb Cartridge Kit BD Multi-Check Control BD Multi-Check CD4 Low Control Eurotrol FACSPresto Hb Control (Levels1-3) Regulation Number: 21 CFR 864.5220 Regulation Name: Automated Differential Cell Counter Regulatory Class: II Product Code: PMG, OYE, GKL, JPK Dated: November 18, 2015 Received: November 19, 2015
Dear Dr. Bessette:
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
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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 as set forth in the quality systems (QS) 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 you desire specific advice for your device on our labeling regulations (21 CFR Parts 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" (21 CFR 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 vours.
Leonthena R. Carrington -S
Leonthena R. Carrington, MS, MBA, MT(ASCP) Director Division of Immunology and Hematology Devices Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health
Enclosure
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Indications for Use
510(k) Number (if known) K150815
Device Name BD FACSPresto System BD FACSPresto CD4/Hb Cartridge BD FACSPresto CD4/Hb Cartridge Kit
Indications for Use (Describe)
BD FACSPresto System:
The BD FACSPresto System is an automated multicolor fluorescent imaging cytometer and absorbance spectrometer to be used in conjunction with single use reagent cartridges in performing the direct cell enumeration and measurement of absorbance spectrums.
· For use with the BD FACSPresto™ CD4/Hb Cartridge and BD FACSPresto™ CD4/Hb Cartridge Kit in the direct quantification and enumeration of CD4 absolute count, CD4 percentage of lymphocytes, and determination of hemoglobin concentration in normal and HIV positive patients, in conjunction with other laboratory and clinical findings.
· For use in children, adolescents, and adults.
· For use with human whole blood from fingerstick and/or venous collections in K2 EDTA blood collection tubes.
· Not for point-of-care use.
· For in vitro diagnostic use.
BD FACSPresto CD4/Hb Cartridge & BD FACSPresto CD4/Hb Cartridge Kit:
The BD FACSPresto CD4/Hb Cartridge is a single use reagent cartridge to be used with the BD FACSPresto™ System for performing the direct quantification and enumeration of CD4 absolute count, CD4 percentage of lymphocytes, and determination of hemoglobin concentration in normal and HIV positive patients, in conjunction with other laboratory and clinical findings.
· For use in children, adolescents, and adults
· For use with human whole blood from fingerstick and/or venous collections in K2 EDTA blood collection tubes.
· Not for point-of-care use.
· For in vitro diagnostic use.
Type of Use (Select one or both, as applicable)
| Prescription Use (Part 21 CFR 801 Subpart D) | ☑ |
|---|---|
| Over-The-Counter Use (21 CFR 801 Subpart C) | ☐ |
CONTINUE ON A SEPARATE PAGE IF NEEDED.
This section applies only to requirements of the Paperwork Reduction Act of 1995.
DO NOT SEND YOUR COMPLETED FORM TO THE PRA STAFF EMAIL ADDRESS BELOW.
The burden time for this collection of information is estimated to average 79 hours per response, including the time to review instructions, search existing data sources, gather and maintain the data needed and complete and review the collection of information. Send comments regarding this burden estimate or any other aspect of this information collection, including suggestions for reducing this burden, to:
Department of Health and Human Services Food and Drug Administration Office of Chief Information Officer Paperwork Reduction Act (PRA) Staff PRAStaff@fda.hhs.gov
"An agency may not conduct or sponsor, and a person is not required to respond to, a collection of information unless it displays a currently valid OMB number."
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Indications for Use
510(k) Number (if known) K150815
Device Name BD Multi-Check Control BD Multi-Check CD4 Low Control
Indications for Use (Describe) BD Multi-Check Control:
The 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.
The BDTM Multi-Check control is also intended as a CD4 and %CD4 process control for antibody staining, instrument performance, and data analysis on the BD FACSPresto™ system, an imaging cytometer.
BD Multi-Check CD4 Low Control:
The 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 data analysis.
The BD™ Multi-Check CD4 low control is also intended as a CD4 and %CD4 process control for antibody staining, instrument performance, and data analysis on the BD FACSPresto™ system, an imaging cytometer.
| Type of Use (Select one or both, as applicable) |
|---|
| ☑ Prescription Use (Part 21 CFR 801 Subpart D) |
| ☐ Over-The-Counter Use (21 CFR 801 Subpart C) |
CONTINUE ON A SEPARATE PAGE IF NEEDED.
This section applies only to requirements of the Paperwork Reduction Act of 1995.
DO NOT SEND YOUR COMPLETED FORM TO THE PRA STAFF EMAIL ADDRESS BELOW.
The burden time for this collection of information is estimated to average 79 hours per response, including the time to review instructions, search existing data sources, gather and maintain the data needed and complete and review the collection of information. Send comments regarding this burden estimate or any other aspect of this information collection, including suggestions for reducing this burden, to:
Department of Health and Human Services Food and Drug Administration Office of Chief Information Officer Paperwork Reduction Act (PRA) Staff PRAStaff(@fda.hhs.gov
"An agency may not conduct or sponsor, and a person is not required to respond to, a collection of information unless it displays a currently valid OMB number."
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Indications for Use
510(k) Number (if known) K150815
Device Name Eurotrol FACSPresto Hb Control
Indications for Use (Describe)
Eurotrol FACSPresto Hb Control is an assayed hemoglobin control intended for in vitro diagnostic use in the verification of the precision and accuracy of the BD FACSPrestoTM System.
| Type of Use (Select one or both, as applicable) | |
|---|---|
| × Prescription Use (Part 21 CFR 801 Subpart D) | □ Over-The-Counter Use (21 CFR 801 Subpart C) |
CONTINUE ON A SEPARATE PAGE IF NEEDED.
This section applies only to requirements of the Paperwork Reduction Act of 1995.
DO NOT SEND YOUR COMPLETED FORM TO THE PRA STAFF EMAIL ADDRESS BELOW.
The burden time for this collection of information is estimated to average 79 hours per response, including the time to review instructions, search existing data sources, gather and maintain the data needed and complete and review the collection of information. Send comments regarding this burden estimate or any other aspect of this information collection, including suggestions for reducing this burden, to:
Department of Health and Human Services Food and Drug Administration Office of Chief Information Officer Paperwork Reduction Act (PRA) Staff PRAStaff@fda.hhs.gov
"An agency may not conduct or sponsor, and a person is not required to respond to, a collection of information unless it displays a currently valid OMB number."
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Section 5 510(k) Summary
This 510(k) summary is being submitted in accordance with the requirements of Safe Medical Devices Act of 1990 and 21 CFR 807.92.
Date of Summary: November 13, 2015
5.1 Submitted By
BD Biosciences 2350 Qume Drive San Jose, CA 95131-1807 USA
Contact: Catherine Bessette Senior Regulatory Affairs Specialist, Regulatory Affairs (408) 954-4109 Telephone: (408) 954-2347 Fax: Catherine M Bessette@BD.com Email:
5.2 Trade Name/Device Name
| Device Name: | BD FACSPresto™ System |
|---|---|
| BD FACSPresto™ CD4/Hb Cartridge | |
| BD FACSPresto™ CD4/Hb Cartridge Kit | |
| Classification: | Class II |
| Regulation Description: | Automated Differential Cell Counter |
| Regulation Medical Specialty: | Hematology |
| Product Code: | PMG |
Regulation: 21 CFR 864.5220
Device Name: BD Multi-Check Control BD Multi-Check CD4 Low Control Classification: Class II Regulation Description: Hematology Quality Control Mixture Regulation Medical Specialty: Hematology Product Code: JPK Regulation: 21 CFR 864.8625
Device Name: Eurotrol FACSPresto Hb Control (Levels 1-3) Classification: Class II Regulation Description: Hematology Quality Control Mixture Regulation Medical Specialty: Hematology Product Code: JPK Regulation: 21 CFR 864.8625
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5.3 Predicate Device
- BD FACSCalibur™ using BD Tritest CD3/CD4/CD45 with BD Trucount . Tubes and BD MultiSet Software (K071141)
- . R&D Systems' Whole Blood Flow Control, also known as StatusFlow (K961610 & BK990005)
- StatusFlow (K982231) ●
- Eurotrol Hb 301 Control (Levels 1-3) (BK030067) ●
5.4 Reference Device - Sysmex System
Sysmex™ Automated Hematology Analyzer KX-21N (K981761)
5.5 Predicate Device and Reference Device Selection Rationale
The FACSCalibur using BD Tritest CD3/CD4/CD45 with BD Trucount Tubes (K071141) was chosen as a predicate since it directly enumerates CD4 and %CD4 on the same specimen types. It is also used to characterize and monitor HIVinfected individuals.
The Sysmex Automated Hematology Analyzer KX-21N (K981761) was chosen as the reference device since it determines hemoglobin concentration on the same specimen type.
StatusFlow and StatusFlow-9 were chosen as a predicate since they are the same reagent composition as the BD branded version of this product, known as BD Multi-Check Control and CD4 Low Control.
Eurotrol Hb 301 Control (Levels 1-3) was chosen as the predicate since they are the same reagent composition as the BD branded version of this product, known as Eurotrol FACSPresto Hb Control (Levels 1-3).
5.6 Basic Description of the Device
The BD FACSPresto System is an accurate, robust, and portable CD4, %CD4, and hemoglobin (Hb) System. The BD FACSPresto System has fluorescence microscopy and light absorbance capabilities. In addition, the instrument has integrated BD FACSPresto Software and instrument quality controls.
The BD FACSPresto CD4/Hb Cartridge contains antibody-fluorophore conjugates dried on a reagent disc and is embedded with reagent quality controls. The cartridge is designed with onboard reagents that mix well into the blood sample, and enumerate cells populations using fluorescence only. The cartridge is designed with fluidic properties that distribute a sufficient volume and sample into the imaging field of view for precise cell counting.
The BD FACSPresto CD4 and %CD4 assays are designed to stain cells with antibody-fluorophore conjugates for three color fluorescence reading using the BD FACSPresto System. CD4 PE-Cy5 stains CD4-positive cells; while CD3-
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APC and CD45RA-APC stains total lymphocytes for use in the %CD4 calculation (CD3 stains T cells, while CD45RA stains B and NK cells in a patented formulation). CD14-PE is used for staining monocytes to exclude CD4 and/or CD45RA expressing monocytes from analysis.
BD Multi-Check Control and BD Multi-Check CD4 Low Control are process controls for the CD4 and %CD4 assay on the BD FACSPresto system. They are composed of human leukocytes and erythrocytes in a stabilizing medium and are intended to be used as a complete process control for antibody staining. instrument performance, and data analysis on the BD FACSPresto system.
The BD FACSPresto Hb assay is performed by a spectrophotometric method. using absorbance at an isobestic point for multiple forms of hemoglobin, with correction for scatter. The cartridge microfluidic channel permits absorbance reading of blood and of a reference area.
Eurotrol FACSPresto Hb Control is used as a process control for the Hb assay on the BD FACSPresto system. It is composed of purified bovine hemolysate and is intended to be used as an assayed hemoglobin process control intended for in vitro diagnostic use in the verification of the precision and accuracy of the BD FACSPresto System.
5.7 Indications for Use
BD FACSPresto System
BD FACSPresto System is an automated multicolor fluorescent imaging cytometer and absorbance spectrometer to be used in conjunction with single use reagent cartridges in performing the direct cell enumeration and measurement of absorbance spectrums.
- For use with the BD FACSPresto™ CD4/Hb Cartridge and BD ● FACSPresto™ CD4/Hb Cartridge Kit in the direct quantification and enumeration of CD4 absolute count, CD4 percentage of lymphocytes, and determination of hemoglobin concentration in normal and HIV positive patients, in conjunction with other laboratory and clinical findings.
- For use in children, adolescents, and adults. ●
- . For use with human whole blood from fingerstick and/or venous collections in K2 EDTA or K3 EDTA blood collection tubes.
- Not for point-of-care use. .
- For in vitro diagnostic use. ●
BD FACSPresto CD4/Hb Cartridge
The BD FACSPresto CD4/Hb Cartridge is a single use reagent cartridge to be used with the BD FACSPresto™ System for performing the direct quantification and enumeration of CD4 absolute count, CD4 percentage of lymphocytes, and
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determination of hemoglobin concentration in normal and HIV positive patients, in conjunction with other laboratory and clinical findings.
- For use in children, adolescents, and adults. .
- For use with human whole blood from fingerstick and/or venous . collections in K2 EDTA or K3 EDTA blood collection tubes.
- Not for point-of-care use. .
- . For in vitro diagnostic use.
BD Multi-Check Control
The BDTM 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.
The BDTM Multi-Check control is also intended as a CD4 and %CD4 process control for antibody staining, instrument performance, and data analysis on the BD FACSPresto™ system, an imaging cytometer.
BD Multi-Check CD4 Low Control
The 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.
The BDTM Multi-Check CD4 low control is also intended as a CD4 and %CD4 process control for antibody staining, instrument performance, and data analysis on the BD FACSPresto™ system, an imaging cytometer.
Eurotrol FACSPresto Hb Control
Eurotrol FACSPresto Hb Control is an assayed hemoglobin control intended for in vitro diagnostic use in the verification of the precision and accuracy of the FACSPresto System.
The Indications for Use statements are similar to the predicate and reference devices. The differences do not affect the safety and effectiveness of the device relative to the predicate and reference devices.
5.8 Comparison to the Predicate and Reference Devices
Similarities/differences tables are provided for the BD FACSPresto system as compared to the BD FACSCalibur system (Table 5-1) and as compared to the Sysmex system (Table 5-2).
Regarding assay methodology, the BD FACSCalibur system utilizes cytometry through flow, while the BD FACSPresto utilizes cytometry through imaging. Although slightly different technologies, both designs function based on the same
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principles. Both assay methods use fluorescently labeled antibodies to specifically label cell populations to classify them into sub-populations used for determining lymphocytes/uL and CD4 lymphocytes/uL. In each case, the sample is illuminated with light that excites the fluorescent labels and emitted light passes through optical filters to measure fluorescence intensity for each cell event.
Like flow cytometry, image cytometry is an event threshold or event based method. In both methods, fluorescence intensity is used to determine whether an object is there or not. The distinguishing features between flow and imaging cytometry are merely that (1) in flow, the sample is flowed in front of the detection system in a narrow fluid stream, while in imaging, the sample is static and spread out over the imaging field of view; and (2) flow cytometry includes light scatter intensity as an additional optical parameter. In either case, analysis algorithms are used to convert information about light intensities in different optical channels into cell 'events' and then further classify those events into cell populations of interest such as CD4 positive or negative lymphocytes.
Thus imaging cytometry, similar to flow cytometry, can be defined as the process of extracting and making sense of cytometric data obtained primarily from fluorescence signal intensities of cells specifically labeled with fluorescent antibodies.
| Feature/Attribute | BD FACSCalibur using BD TritestCD3/CD4/CD45 with BD TrucountTubes (Predicate Device, K071141) | BD FACSPresto System for use withBD FACSPresto CD4/Hb Cartridgeand BD FACSPresto CD4/HbCartridge Kit (Subject Device) |
|---|---|---|
| Intended Use/Indications forUse | • For use with any flow cytometer equippedwith a 488 nm laser and capable ofdetection in the ranges: 510-545 nm, 562-607 nm, and >650 nm• For use in erythrocyte-lysed wholeperipheral blood• For use with or without isotype control• To characterize and monitor some formsof autoimmune disease• To characterize and monitor some formsof immunodeficiency disease, such as inHIV-infected individuals | BD FACSPresto System is an automatedmulticolor fluorescent imaging cytometerand absorbance spectrometer to be used inconjunction with single use reagentcartridges in performing the direct cellenumeration and measurement ofabsorbance spectrums.• For use with the BD FACSPrestoTMCD4/Hb Cartridge and BDFACSPrestoTM CD4/Hb Cartridge Kitin the direct quantification andenumeration of CD4 absolute count,CD4 percentage of lymphocytes, anddetermination of hemoglobinconcentration in normal and HIVpositive patients, in conjunction withother laboratory and clinical findings.• For use in children, adolescents, andadults.• For use with human whole blood fromfingerstick and/or venous collections inK2 EDTA or K2 EDTA blood collection |
| Feature/Attribute | BD FACSCalibur using BD TritestCD3/CD4/ CD45 with BD TrucountTubes (Predicate Device, K071141) | BD FACSPresto System for use withBD FACSPresto CD4/Hb Cartridgeand BD FACSPresto CD4/HbCartridge Kit (Subject Device) |
| tubes.• Not for point-of-care use.• For in vitro diagnostic use. | ||
| The BD FACSPresto CD4/Hb Cartridgeis a single use reagent cartridge to be usedwith the BD FACSPresto™ System forperforming the direct quantification andenumeration of CD4 absolute count, CD4percentage of lymphocytes, anddetermination of hemoglobinconcentration in normal and HIV positivepatients, in conjunction with otherlaboratory and clinical findings. | ||
| • For use in children, adolescents, andadults.• For use with human whole blood fromfingerstick and/or venous collections inK2 EDTA or K3 EDTA blood collectiontubes.• Not for point-of-care use.• For in vitro diagnostic use. | ||
| DeviceClassificationand ProductCode | Differential Cell Counter• Regulation Number:21 CFR 864.5220• Product Code: GKZ | Automated Differential Cell Counter• Regulation Number:21 CFR 864.5220• Product Code: PMG |
| AssayMethodology | Cytometry (flow) | Cytometry (imaging) |
| Assay Menu(FDA ClearedAssays) | Absolute CD4 count%CD4 | Same |
| ResultsReporting | • Absolute CD4 count (cells/uL)• %CD4 (the percentage of CD4 positivelymphocytes counted within the totallymphocyte population count) | Same |
| Sample Type | Whole blood | Same |
| SampleVolume | Minimum 100 uL whole blood | 1-2 drops venous or capillary wholeblood |
| SamplePreparation | Manual pipetting for the lyse/wash orlyse/no-wash methods, or automated withthe BD FACS Sample Prep Assistant (SPA)for the lyse/no-wash method | Manual introduction of venous orcapillary blood onto BD FACSPrestoCartridge |
| SampleAnalysis | • A controlled quantity of fluorescent beadsis included in the sample throughpreparation in BD TruCount tubes to | • Capillary chamber height is preciselymeasured in manufacturing for eachcartridge and encoded in the cartridgebarcode. The size of the analysis image |
| Feature/Attribute | BD FACSCalibur using BD TritestCD3/CD4/ CD45 with BD TrucountTubes (Predicate Device, K071141) | BD FACSPresto System for use withBD FACSPresto CD4/Hb Cartridgeand BD FACSPresto CD4/HbCartridge Kit (Subject Device) |
| determine the volume of sample analyzed.• Fluorescence intensity of beads and ofcells of interest labeled by specificfluorescent antibodies is quantitativelymeasured.• Cells and fluorescent beads arealgorithmically classified based on thesesignal intensities.• The number of cells in each classificationand the volume of sample analyzed are usedto calculate the reported assay results. | areas is determined by the instrument.The two are used to calculate the volumeof analyzed sample.• Fluorescence intensity of cells ofinterest labeled by specific fluorescentantibodies is quantitatively measured.• Cells are algorithmically classifiedbased on these signal intensities.• The number of cells in eachclassification and the volume of sampleanalyzed are used to calculate thereported assay results. | |
| AssayPrinciples | CD4 and %CD4 flow cytometry assaysusing a 3 color direct immunofluorescentreagent to identify cell subset populations inlysed blood with automated analysis.Trucount beads are used for volumedetermination. | CD4 and %CD4 imaging cytometryassays using a 3-color directimmunofluorescent reagent to identifycell subset populations in whole bloodwith automated analysis. Precisedimensions of microfluidic channel andimage area are used for volumetricdetermination. |
| OpticsPrinciples -CD4and %CD4 | Fluorescence excitation of stained cells inflow stream by laser illumination;Fluorescence emission measured by PMTs | Fluorescence excitation of stained cells inmicrofluidic channel by LEDillumination;Fluorescence emission measured by CCDcamera imaging |
| Fluidics | Consists of a pinch valve assembly whichcontrols the flow of sample, saline sheathfluid, and waste fluids during dataacquisition. | Cartridge contains a microfluidic channelthrough which the sample fills bycapillary action. After filling completes,sample is static during data acquisition. |
| InstrumentSetup andQualityControl | Setup: Semi-automated setup using BDFACSComp software with BD Calibritebeads for setting PMT voltages,fluorescence compensation, and checkinginstrument sensitivity. | Setup: Automated instrument setup.Instrument QC: automated verification ofinstrument performance at power-on-self-test (POST) and during cartridge runs.Cartridge QC: rat anti-mouse antibodiesbound to polystyrene beads confirmpresence of sample and reagent. |
| Software | Integrated software on instrument and BDMultiSet Software on external computer | Integrated BD FACSPresto Software |
| Feature/Attribute | Sysmex Automated Hematology AnalyzerKX-21N (Reference Device, K981761) | BD FACSPresto System for use withBD FACSPresto CD4/Hb Cartridgeand BD FACSPresto CD4/HbCartridge Kit (Subject Device) |
| Intended Use/Indications forUse | The intended use of the Sysmex KX-21 isas an automated cell counter for in vitrodiagnostic use in clinical laboratories. | BD FACSPresto System is an automatedmulticolor fluorescent imaging cytometerand absorbance spectrometer to be used inconjunction with single use reagentcartridges in performing the direct cellenumeration and measurement ofabsorbance spectrums.• For use with the BD FACSPrestoTMCD4/Hb Cartridge and BDFACSPrestoTM CD4/Hb Cartridge Kitin the direct quantification andenumeration of CD4 absolute count,CD4 percentage of lymphocytes, anddetermination of hemoglobinconcentration in normal and HIVpositive patients, in conjunction withother laboraotry and clinical findings.• For use in children, adolescents, andadults.• For use with human whole blood fromfingerstick and/or venous collections inK2 EDTA or K3 EDTA blood collectiontubes.• Not for point-of-care use.• For in vitro diagnostic use.The BD FACSPresto CD4/Hb Cartridgeis a single use reagent cartridge to be usedwith the BD FACSPrestoTM System forperforming the direct quantification andenumeration of CD4 absolute count, CD4percentage of lymphocytes, anddetermination of hemoglobinconcentration in normal and HIV positivepatients, in conjunction with otherlaboratory and clinical findings.• For use in children, adolescents, andadults.• For use with human whole blood fromfingerstick and/or venous collections inK2 EDTA or K3 EDTA blood collectiontubes.• Not for point-of-care use.• For in vitro diagnostic use. |
| Feature/Attribute | Sysmex Automated Hematology AnalyzerKX-21N (Reference Device, K981761) | BD FACSPresto System for use withBD FACSPresto CD4/Hb Cartridgeand BD FACSPresto CD4/HbCartridge Kit (Subject Device) |
| DeviceClassificationand ProductCode | Automated Cell Counter (Particle Counter)• Regulation Number:21 FR 864.5200• Product Code: GKL and GKZ | Automated Differential Cell Counter• Regulation Number:21 FR 864.5220• Product Code: PMG |
| AssayMethodology | Absorbance spectrophotometry | Same |
| Assay Menu(FDA ClearedAssays) | Hb determination | Same |
| ResultsReporting | Total Hb concentration | Same |
| Sample Type | Whole blood | Same |
| SampleVolume | 50 µL whole blood40 µL pre-dilute | 1-2 drops venous or capillary wholeblood |
| SamplePreparation | Manual placement of blood tube ontosample aspiration arm | Manual introduction of venous orcapillary blood onto BD FACSPrestoCartridge |
| SampleAnalysis | • Narrow-spectrum LED light is directedthrough the blood sample to measure lightabsorbance at a hemoglobin-absorbingwavelength.• Sodium lauryl sulfate lyses the blood cellsin the sample, eliminating light attenuationcaused by scatter.• Absorbance at the LED wavelength isused to calculate hemoglobin concentration. | • Broad-spectrum LED light is directedthrough the blood sample and adiffraction grating to create a spectrumand measure light absorbance at 2wavelengths: a hemoglobin isosbesticpoint and a non-hemoglobin-absorbingpoint.• The light absorbance in the non-hemoglobin-absorbing region measuresthe amount of light attenuation due toscatter.• Absorbance at the isosbestic point iscorrected for scatter and used to calculatehemoglobin concentration. |
| AssayPrinciples | Photometric method with reagent thatreleases hemoglobin from red cells andforms a stable colored complex. | Photometric method that detects thepresence of predominant forms of Hb,with correction for scatter. |
| OpticsPrinciples - Hb | Absorbance photometric method usingLED-generated monochromatic light and aphotosensor | Absorbance spectrophotometric methodusing LED-generated broad spectrumlight, diffraction grating, and CCD sensor |
| Fluidics | A vacuum pump aspirates sample blood,which passes through a rotor valve and thento volumetric dispensing, mixing, rinsing,and draining. Sample is flowing duringdata acquisition. | Cartridge contains a microfluidic channelthrough which the sample fills bycapillary action. After filling completes,sample is static during data acquisition. |
| InstrumentSetup andQuality | Setup: Automated startup check.Instrument QC: Levey -Jennings controlthat uses data from a single analysis of | Setup: Automated instrument setup.Instrument QC: automated verification of |
| Feature/Attribute | Sysmex Automated Hematology AnalyzerKX-21N (Reference Device, K981761) | BD FACSPresto System for use withBD FACSPresto CD4/Hb Cartridgeand BD FACSPresto CD4/HbCartridge Kit (Subject Device) |
| Control | control sample (Sysmex Eight-Check 3WPX-Tra Controls). | test (POST) and during cartridge runs. |
| Software | Integrated Sysmex Software | Integrated BD FACSPresto Software |
Table 5-1: Similarities/Differences - Predicate Device (BD FACSCalibur system using Tritest) against Subject Device (BD FACSPresto System) for Absolute CD4 Count and %CD4 Assays.
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Table 5-2: Similarities/Differences –Reference (Sysmex Automated Hematology Analyzer KX-21N) against Subject Device (BD FACSPresto System) for total Hb assay.
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Table 5-3: Similarities/Differences – Predicate Device (R&D Systems' Whole Blood Flow Control) against Subject Device (BD Multi-Check Control)
| Feature/Attribute | R&D Systems' Whole Blood FlowControl (aka StatusFlow)(Predicate Device, K961610 &BK990005) | BD Multi-Check Control(Subject Device) |
|---|---|---|
| Intended Use/Indications forUse | R&D Systems' Whole Blood Flow Control(WBFC) is a stabilized preparation ofhuman peripheral leukocytes anderythrocytes to be used as a control in thecomplete immunophenotyping processwhich includes: antibody staining, RBClysis, instrument set-up and instrumentperformance. | The BD Multi-Check control is intendedas a complete process control forimmunophenotyping by flow cytometry.It is a control for antibody staining, redblood cell (RBC) lysis, instrument setup,instrument performance, and dataanalysis.The BD Multi-Check control is alsointended as a CD4 and %CD4 processcontrol for antibody staining, instrumentperformance, and data analysis on the BDFACSPresto system, an imagingcytometer. |
| Product Code | GKZ | JPK |
| Composition | Human leukocytes and erythrocytes in astabilizing medium. | Same |
| StorageConditions | 2-8°C | Same |
| Open VialStability | 9 thermal cycles | Same |
| Closed VialStability | 45 days | Same |
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Table 5-4: Similarities/Differences – Predicate Device (StatusFlow4) against Subject Device (BD Multi-Check CD4 Low Control)
| Feature/Attribute | StatusFlowLo(Predicate Device, K982231) | BD Multi-Check CD4 Low Control(Subject Device) |
|---|---|---|
| Intended Use/Indications forUse | StatusFlowLo is intended as a completeprocess control for immunophenotyping byflow cytometry. It is a control for antibodystaining, RBC lysis, instrument set-up,instrument performance and data analysis. | The BD Multi-Check CD4 low controlis intended as a complete process controlfor immunophenotyping by flowcytometry. It is a control for antibodystaining, red blood cell (RBC) lysis,instrument setup, instrumentperformance, and data analysis.The BD Multi-Check CD4 low control isalso intended as a CD4 and %CD4process control for antibody staining,instrument performance, and data analysison the BD FACSPresto system, animaging cytometer. |
| Product Code | GKZ | JPK |
| Composition | Human leukocytes and erythrocytes in astabilizing medium. | Same |
| StorageConditions | 2-8°C | Same |
| Open VialStability | 9 thermal cycles | Same |
| Closed VialStability | 45 days | Same |
Table 5-5: Similarities/Differences – Predicate Device (Eurotrol Hb 301 Control) against Subject Device (Eurotrol FACSPresto Hb Control)
| Feature/Attribute | Eurotrol Hb 301 Control(Predicate Device, BK030067) | Eurotrol FACSPresto Hb Control(Subject Device) |
|---|---|---|
| Intended Use/Indications forUse | The Eurotrol 301 Hb Control is an assayedhemoglobin control intended forprofessional use in the verification of theprecision and accuracy of the HemoCue Hb301 System. | The Eurotrol FACSPresto Hb Control isan assayed hemoglobin control intendedfor in vitro diagnostic use in theverification of the precision andaccuracy of the BD FACSPrestoSystem. |
| Product Code | GGM | JPK |
| Composition | Purified bovine hemolysate | Same |
| Open VialStability | 30 days at 2-30°C | 30 days at 2-8°C |
| Closed VialStability | 25 months at 2-8°C | 1 month at 2-8°C |
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5.9 Bench and Clinical Performance Data
The following bench performance data (Table 5-6) were provided in support of the substantial equivalence determination.
| PerformanceCharacteristic | Standard | Results |
|---|---|---|
| MethodComparison | Based on MethodComparison and BiasEstimation Using PatientSamples, CLSI documentEP9-A2-IR. | All method comparison results met study acceptancecriteria. The BD FACSPresto system provided CD4and %CD4 results (VP, N = 107 and FS, N = 84) thatare substantially equivalent to those generated by thepredicate system. The BD FACSPresto systemprovided Hb results (VP, N = 84 and FS, N = 108) thatare substantially equivalent to those generated by thereference system. |
| Precision | Based on Evaluation ofPrecision Performance ofQuantitative Measurement,CLSI document EP5-A2. | The BD FACSPresto system demonstrates acceptableCV and/or SD results for within-run and total precisionfor CD4, %CD4, and Hb measured using Streck CD-Chex Plus (Normal and CD4-Low) (N = 168) andEurotrol FACSPresto Hb Controls (Levels 1-3) (N =252) on the BD FACSPresto system. |
| Linearity | Based on Evaluation of theLinearity of QuantitativeMeasurement Procedures: AStatistical Approach, CLSIdocument EP6-A. | The verification test results for the BD FACSPrestosystem demonstrate acceptable linearity for CD4,Lymphocyte, and Hb ranges (N = 33 for each).The dynamic range of the BD FACSPresto system isestablished to be linear within $42-4872$ CD4 cells/ $µL$ .The dynamic range of the BD FACSPresto system isestablished to be linear within $124-10,713$ Lymphocytecells/ $µL$ .The dynamic range of the BD FACSPresto system isestablished to be linear within $2-26$ Hb g/dL. |
| HemoglobinAssayTraceability | Based on Reference andSelected Procedures for theQuantitative Determinationof Hemoglobin in Blood,CLSI document H15-A3 | This study concludes that the BD FACSPresto systemHb assay is traceable to the HiCN method forhemoglobin determination (N = 4-20 depending onbin). The Hb assay is linear and accurate across thereported linear range (2-20 g/dL) as compared to theHiCN method. |
| AnalyticalSensitivity | Based on Protocols forDetermination of Limits ofDetection and Limits ofQuantitation, CLSI documentEP17-A | From this CD4 evaluation, the LoD is determined to be$22$ cells/ $uL$ (N = 60) and the LoQ is determined to be$35$ cells/ $uL$ (N=180). This LoD value is below thesystem's claimed range for CD4. From this Hbevaluation, the LoD is determined to be $0.91$ g/dL(N=300) and the LoQ is determined to be $2$ g/dL (N =60), which supports the claimed range of 2-20 g/dL. |
Table 5-6: Bench Performance Summary
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| PerformanceCharacteristic | Standard | Results |
|---|---|---|
| Interference | Based on InterferenceTesting in ClinicalChemistry , CLSI documentEP7-A2. | Of the 34 analytes tested, there was no clinicallysignificant interference at the maximum concentrationstested for 33 of them. One analyte (Gamma Globulin)demonstrated interference at the maximumconcentration, but not the mid and low concentrations.None of the analytes caused a bias of > 15% with CD4,%CD4, and Hb assays in the BD FACSPrestoCartridge at the concentrations to be reported. |
| SpecimenStability - Ageof Blood / Ageof Stain | Based on Procedures andDevices for the Collection ofDiagnostic Capillary BloodSpecimens , CLSI documentH04-A6 | The acceptance criteria were met for all parameters.The Stability Evaluation study supports one (1) hourstain for both venous and capillary blood, and the 22-hour age of blood for venous blood only (N = 70). |
| Biocompatibility | • ANSI/AAMI/ISO 10993-5:2009, BiologicalEvaluation of MedicalDevices-Part 5: Test for invitro cytotoxicity• ASTM F2148:2007 –Standard Practice forEvaluation of DelayedContact hypersensitivityusing the Murine LocalLymph Node Assay(LLNA)• ANSI/AAMI/ISO 10993-10:2010, BiologicalEvaluation of MedicalDevices-Part 10: Tests forirritation and skinsensitization | In the 48-hour titration cytotoxicity / elution test, thetest article passed based on reactions observed. Thetest article met the requirements of the test, since thecultures treated with the extract showed no reactivity.In the murine local lymph node assay, the grouptreated with the test article elutes showed a StimulationIndex <3 compared to that of the negative control. Thetest article met the requirements of the test and isconsidered to be a non-sensitizer in mice.In the primary dermal irritation study, a PII score of 0meant that the test article is considered to be anegligible irritant in rabbits. |
| EMC | • IEC 61326-1:2012• IEC61326-2-6:2012• IEC 61000-3-2:2005• IEC 61000-3-3:2008 | EMC testing was conducted on the BD FACSPrestoSystem. The system complies with the IECs standardslisted. |
| Electrical Safety | • UL 61010-1:2004• IEC 61010-2-081:2002• IEC 61010-2-101:2009 | Electrical safety testing was conducted on the BDFACSPresto System. The system complies withstandards listed. |
| BD Multi-Checkcontrols - ValueAssignmentVerification | N/A | FACSPresto-assigned ranges were established for 3lots of BD Multi-Check Control and CD4 Low Controlusing 3 instruments and 3 lots of Cartridges. Datacollected on 3 instruments after 18 minutes and 2hours of incubation on the Cartridge. All data pointsfell within the FACSPresto-assigned ranges. |
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| PerformanceCharacteristic | Standard | Results |
|---|---|---|
| BD Multi-Checkcontrols -Precision | Based on Evaluation ofPrecision Performance ofQuantitative Measurement,CLSI document EP5-A3. | The BD Multi-Check Control and CD4 Low Controldemonstrate acceptable SD and/or CV results forwithin-run, between-run, and total precision for CD4and %CD4 measurements on the BD FACSPrestosystem. A total of 21 days and 9 open/close thermalcycles were executed for each process control lot at 3sites and each cartridge was read within 18-30 minutesof incubation. The results of this study, with upper97.5% confidence interval, all pass the acceptancecriteria. |
| EurotrolFACSPresto HbControl - ValueAssignmentVerification | N/A | FACSPresto-assigned ranges were established for 3lots of each of 3 levels with a replicate of N=9. Datacollected both in-house and at 3 clinical sites wereorganized into three distinct sets of Level 1, Level 2,and Level 3. All data points fell within theFACSPresto-assigned ranges. |
| EurotrolFACSPresto HbControl -Precision | Based on Evaluation ofPrecision Performance ofQuantitative Measurement,CLSI document EP5-A2. | The Eurotrol FACSPresto Hb Control demonstratesacceptable CV results for within-run, between-run, andtotal precision for Hb measurements on the BDFACSPresto system. Each cartridge was read at 3different stain times of 1-5 minutes, 18-30 minutes and2 hours (+/- 15 min) for a total of 240 readings per lot.With 9 lots of controls (3 lots per level), the totalnumber of cartridges was 720 and the total number ofreadings with 3 stain times was 2160. |
The following clinical performance data (Table 5-7) were provided in support of the substantial equivalence determination.
Table 5-7: Clinical Performance Summary
| PerformanceCharacteristic | Standard | Results |
|---|---|---|
| MethodComparison | Based on MethodComparison and BiasEstimation Using PatientSamples, CLSI documentEP9-A2-IR. | De-identified and delinked prospectively enrollednormal and HIV infected subjects from 8 clinical siteswere studied (N=796 venous and N=692 capillary).The acceptance criteria for CD4, %CD4, and Hb invenous and capillary whole blood on the BDFACSPresto system were successfully met both for allsites. No adverse effects or complications wereobserved. |
| PerformanceCharacteristic | Standard | Results |
| Precision | Based on Evaluation ofPrecision Performance ofQuantitative Measurement,CLSI document EP5-A2. | The precision evaluation of the BD FACSPrestosystem was conducted at one clinical site. Theevaluation included analysis for both precisionreproducibility and repeatability. Precisionreproducibility measured operator and instrumentvariability. Site-to-site reproducibility was carried outat three clinical sites. The acceptance criteria forprecision repeatability, reproducibility, and site-to-sitereproducibility requirements were met forCD4, %CD4, and Hb. |
| Linearity | Based on Evaluation of theLinearity of QuantitativeMeasurement Procedures: AStatistical Approach, CLSIdocument EP6-A. | The study was carried out at a single site usingprospectively procured specimens tested on the BDFACSPresto system. For each parameter, low and highconcentration pools were created from a specimen, andthen the pools were proportionally mixed to achieveeleven concentrations over a range that was 20-30%wider than the anticipated claim range in addition tothe CD4 medical decision point. The acceptancecriteria for CD4, Lymphocytes, and Hb in the BDFACSPresto system linearity evaluation weresuccessfully passed. Results support the linearityproduct claims. |
| Sample Stability | Based on Procedures andDevices for the Collection ofDiagnostic Capillary BloodSpecimens, CLSI documentH04-A6 | The BD FACSPresto system acceptance criteria forCD4, %CD4, and Hb in venous and capillary sampleswere successfully passed. Results from the stabilityevaluation support the product claims for 1 hourstaining for both capillary and venous specimen typesand up to 22 hours of venous blood storage. |
| ReferenceIntervals | Based on Defining,Establishing and VerifyingReference Intervals in theClinical Laboratory, CLSIdocument EP28-A3c. | The objective of the study was to establish theCD4, %CD4, and Hb reference intervals in a normalreference cohort free of hematology abnormalitiesusing the BD FACSPresto system in prospectivelyprocured venous and capillary blood specimens undervoluntary informed consent from adults. The finalreference ranges are partitioned by parameter andgender. |
| BD Multi-CheckControlValidation | N/A | Clinical Validation data was collected at 3 clinical trialsites to validate that the BD Multi-Check Control andCD4 Low Control fell within the FACSPresto-specificranges. Testing at each site was performed for aminimum of 20 days. The study design incorporatedat least 3 different lots of controls, instruments, andreagents. Precision of the daily runs were analyzed tomonitor the control stability over time. At least 95%of the data points fell within the FACSPresto-assignedranges. |
| PerformanceCharacteristic | Standard | Results |
| EurotrolFACSPresto HbControlValidation | N/A | Clinical Validation data was collected at 3 clinical trialsites to validate that the Eurotrol FACSPresto Hbcontrols fall within the FACSPresto-specific ranges.Testing at each site was performed over 10 days using3 different lots of Eurotrol FACSPresto Hb controlsper level, one lot of levels 1, 2, 3 assigned per site,using one instrument at each site with one cartridgelot. Testing was done in two runs separated by aminimum of 2 hours, using duplicate samples of thethree levels of Eurotrol. Precision of the daily runswere analyzed to monitor the control stability overtime. All data points fell within the FACSPresto-assigned ranges. |
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Based on the performance data from the bench and clinical sites, the BD FACSPresto system was found to have a safety and effectiveness profile that is similar to the predicate and reference devices and raises no new issues of safety and effectiveness.
5.10 Conclusion
Based on the similar principles of operation, bench performance data, and clinical performance data, the BD FACSPresto system is substantially equivalent to the predicate BD FACSCalibur system and to the reference Sysmex system. The process controls, namely the BD Multi-Check Control and CD4 Low Control and to the Eurotrol FACSPresto Hb Controls, are substantially equivalent to the predicate StatusFlow, StatusFlow-9, and Eurotrol Hb 301 Control, respectively.
§ 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.”