ADAMII CD34 System
Device Facts
| Record ID | BK231031 |
|---|---|
| Device Name | ADAMII CD34 System |
| Applicant | NanoEntek, Inc. Korea |
| Product Code | GKZ · Hematology |
| Decision Date | Jun 5, 2024 |
| Decision | SESE |
| Regulation | 21 CFR 864.5220 |
| Device Class | Class 2 |
Indications for Use
ADAMII CD34 System includes ADAMII-CD34 Kit which is designed for use with ADAMII (Instrument), a benchtop image-based fluorescence cell counter. ADAMII CD34 System provides enumeration of viable CD34+ cells, viable CD45+ cells, and calculates percentage of viable CD34+ cells out of viable CD45+ cells. ADAMII CD34 System can be used for mobilized peripheral blood (MPB) collected in Na-Heparin or EDTA, haematopoietic progenitor cell – apheresis (HPC-A) collected in ACD or ACD+Heparin, fresh cord blood (FCB) collected in CPD, and thawed frozen cord blood (TFCB) collected in CPD and stored with 10% DMSO, 1% Dextran 40. ADAMII CD34 System is intended for use in clinical laboratories and for in vitro diagnostic use only. It is not intended for use in point-of-care settings.
Device Story
ADAMII CD34 System is a benchtop image-based fluorescence cell counter for clinical laboratories. It processes samples stained with fluorescence-labeled antibodies and nucleic acid dyes; RBC lysis buffer is used to remove erythrocytes. The instrument uses LED-induced fluorescence (4-channel: Bright field, PE, FITC, PerCP) and a high-sensitivity monochrome CCD camera to acquire images of assay slides. ADAMII software controls hardware, manages data, and performs image analysis to quantify viable CD34+ and CD45+ cell concentrations. Results are displayed and saved for clinical review. The system aids in hematopoietic stem cell enumeration, supporting clinical decision-making regarding stem cell transplantation or collection. It provides automated, standardized quantification compared to manual methods, benefiting patients by ensuring accurate cell counts for therapeutic procedures.
Clinical Evidence
Performance evaluated via method comparison and precision studies. Method comparison (N=913) against predicate showed high correlation (R²=0.99 for CD34, 0.98 for %CD34, 0.99 for CD45). Mean relative bias for CD34 was 0.81% (95% CI: 0.17% to 1.46%). Precision studies across three sites for fresh and thawed cord blood showed CVs ranging from 8.23% to 22.82% for CD34 and 2.43% to 12.56% for CD45. Linearity established for CD34 (1-120 cells/μL for cord blood).
Technological Characteristics
Benchtop image-based fluorescence cell counter. 4-channel (Bright field, PE, FITC, PerCP) imaging platform. Light sources: Green LED (525nm), Blue LED (488nm). Detection: High-sensitivity monochrome CCD. Dimensions: 30W x 42D x 37H cm. Weight: 19.3 kg. Connectivity: Laptop-based software for data management and hardware control. Complies with EN 61010-1, EN 61010-2-081, EN 61010-2-101, EN 61326-1, and EN 61326-2-6.
Indications for Use
Indicated for enumeration of viable CD34+ and CD45+ cells and calculation of %CD34+ in CD45+ population in mobilized peripheral blood, HPC-A, fresh cord blood, and thawed frozen cord blood samples in clinical laboratory settings.
Regulatory Classification
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.
Special Controls
*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.”
Predicate Devices
- BD Stem Cell Enumeration Kit (BK210652)
Submission Summary (Full Text)
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# **Traditional 510(k) Summary**
(in accordance with 21 CFR §807.92)
# **A. Applicant**
Company Name: NanoEntek, Inc.
Address: 12F, 5, Digital-Ro 26-
Gil Guro-Gu
Seoul, KR 08389
Contact Person: Jason Jeong
Phone Number: +82-2-6220-7887
Facsimile Number: +82-2-6220-7999
# **B. Contact Person**
Company Name: Donna Cole
Address: USAContact Person: Donna Cole
Title: Consultant
# **C. Date Prepared: December 1, 2023**
# **D. Trade name: ADAMII CD34 System**
**Classification name:** Automated Differential Cell Counter
**Classification:** 21 CFR §864.5220, Product code(s) GKZ, OYE, Class II
# **E. Predicate device:** BD Stem Cell Enumeration Kit (BK210652) for use on
BD flow cytometers (FACS Lyrics and FACS Calibur)
# **F. Indications for Use:**
ADAMII CD34 System includes ADAMII-CD34 Kit which is designed for use with ADAMII (Instrument), a benchtop image-based fluorescence cell counter. ADAMII CD34 System provides enumeration of viable CD34+ cells, viable CD45+ cells, and calculates percentage of viable CD34+ cells out of viable CD45+ cells. ADAMII CD34 System can be used for mobilized peripheral blood (MPB) collected in Na-Heparin or EDTA, haematopoietic progenitor cell – apheresis (HPC-A) collected in ACD or ACD+Heparin, fresh cord blood (FCB) collected in CPD, and thawed frozen cord blood (TFCB) collected in CPD and stored with 10% DMSO, 1% Dextran 40. ADAMII CD34 System is intended for use in clinical laboratories and for in vitro diagnostic use only. It is not intended for use in point-of-care settings.
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# Device Description
ADAMII-CD34 Kit utilizes fluorescence-labeled antibodies and nucleic acid staining dye to quantify absolute counts (cells/μL) of viable CD34+ hematopoietic cells and the percentage of viable CD34+ out of viable CD45+ cells. The purpose of this 510(k) is to add new sample types to BK18023; fresh and thawed frozen cord blood.
ADAMII-CD34 Kit includes the following components:
ADAMII-CD34 Reagent solution
ADAMII Calibration bead solution
RBC Lysis Buffer (10X)
ADAMII Assay slides
ADAMII (Instrument) is an image-based fluorescence cell counter supplied with a laptop pre-installed with ADAMII-CD34 software. ADAMII (Instrument) is a 4-channel (Bright field, PE, FITC and PerCP) bench-top imaging platform equipped with state-of-the-art optics and a slide holder that accepts ADAMII Assay Slide. ADAMII (Instrument) is based on quantitative fluorometric assay technology capable of quantifying single or multiple fluorophore(s) by measuring LED-induced fluorescence from stained cells. ADAMII Software controls graphical user interface, communication with hardware, database management and data analysis. The software also controls the mechanical components including motors, light sources, and acquisition of images from CCD camera. After completion of image acquisition, ADAMII Software displays and saves results. Final results include (1) Viable CD34+ cells [/μL], (2) Viable CD45+ cells [/μL], (3) Total CD34+ cells [/μL], (4) Total CD45+ cells [/μL], (5) CD34 Viability [%], (6) CD45 Viability [%], (7) the ratio of Viable CD34+ out of Viable CD45 [%].
# G. Substantial Equivalence Discussion
An overview of the similarities and differences between the ADAMII-CD34 Kit and the predicate is provided in the Tables 1 – 3 below.
Table 1 General
| | Subject Device ADAMII CD34 System | Predicate Device BD Stem Enumeration Kit BK210652 |
| --- | --- | --- |
| Indications for Use | ADAMII CD34 System includes ADAMII-CD34 Kit which is designed for use with ADAMII (Instrument), a benchtop image-based fluorescence cell counter. ADAMII CD34 System provides enumeration of viable CD34+ cells, viable CD45+ cells, and calculates percentage of viable CD34+ cells out of viable CD45+ cells. ADAMII CD34 System can be used for mobilized peripheral blood (MPB) collected in Na-Heparin or EDTA, haematopoietic progenitor cell – | The BD® Stem Cell Enumeration Kit is intended for enumeration of viable dual positive CD45+/CD34+ hematopoietic stem cell populations to determine absolute counts (cells/μL) of viable CD34+ and the percentages of viable CD45+/CD34+ hematopoietic stem cells (%CD34). The following cellular-based products (specimens) can be analyzed with this kit: • Normal and mobilized peripheral blood |
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| | apheresis (HPC-A) collected in ACD or ACD+Heparin, fresh cord blood (FCB) collected in CPD, and thawed frozen cord blood (TFCB) collected in CPD and stored with 10% DMSO, 1% Dextran 40. ADAMII CD34 System is intended for use in clinical laboratories and for in vitro diagnostic use only. It is not intended for use in point-of-care settings. | • Fresh and thawed leukapheresis products • Fresh and thawed bone marrow • Fresh and thawed cord blood The kit is intended for in vitro diagnostic (IVD) use on any of the following flow cytometer systems: • BD FACSLyric™ flow cytometer using BD FACSuite™ Clinical application • BD FACSCanto™ II flow cytometer using BD FACSCanto™ clinical software • BD FACSCalibur™ flow cytometer using BD CellQuest™ or BD CellQuest™ Pro software |
| --- | --- | --- |
| Principle Method/Technology | This assay is performed by staining the sample with the reagent and loaded into an individual ADAMII assay slide for absolute counts. When a sample is mixed with reagent, the fluorochrome labeled antibodies and nucleic acid dyes bind specifically to the cell surface and dead cell nucleic acids. Lysis buffer is added to lyse erythrocytes before the sample is loaded into an assay slide. The slide is placed on the precision stage of ADAMII (Instrument), an image-based fluorescence cell counter. After acquiring images and analyzing them, the concentrations of viable CD34+ cells and viable CD45+ cells, and the percentage of viable CD34+ cells in viable CD45+ cell population are calculated. | The single-tube assay is performed by staining the sample with the reagent in individual BD Trucount™ tubes for absolute counts. When a sample is added to the reagent, the fluorochrome-labeled antibodies in the reagent bind specifically to the cell surface. Additionally, the lyophilized pellet in the BD Trucount™ tubes dissolves, releasing a known number of fluorescent beads. The dye 7-AAD is added to assess viability of the cells. Cells that are 7-AAD+ are not viable. Ammonium chloride is added to lyse erythrocytes before the sample is acquired on a flow cytometer. During analysis of the sample, the concentration of viable CD34+ cells and viable CD45+ cells, and the percentage of viable CD34+ cells in the viable CD45+ cell population, are calculated. |
Table 2 Reagent Kits and Sample
| | Subject Device ADAMII-CD34 Kit | Predicate Device BD Stem Cell Enumeration Kit |
| --- | --- | --- |
| Sample type/anticoagulants | • Mobilized peripheral blood (MPB) collected in Na-Heparin or EDTA • Haematopoietic progenitor cell – apheresis (HPC-A) collected in ACD or ACD+Heparin • Fresh cord blood collected in CPD • Thawed frozen cord blood collected in CPD and stored with 10% DMSO and 1% Dextran 40. | • Normal and mobilized peripheral blood collected with either EDTA, ACD-A, heparin, or CPD anticoagulants • Fresh and thawed leukapheresis products collected with a mixture or single source of EDTA, ACD-A, or heparin anticoagulants • Fresh and thawed bone marrow collected with either EDTA, ACD-A, or heparin anticoagulants • Fresh and thawed cord blood collected with either EDTA, ACD-A, heparin, or CPD anticoagulants |
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| Parameters in: ADAMII Indications for Use/ BD Principle/Methods | Viable CD34 cells/μL Percentage of viable CD34 of viable CD45 Viable CD45 cells/μL | Viable CD34 cells/μL Percentage of viable CD34 of viable CD45 Viable CD45 cells/μL |
| --- | --- | --- |
| Other parameters measured and outputted^{1} | Total CD34 cells/μL CD34 viability % Total CD45 cells/μL CD45 viability % | Total CD34 cells/μL CD34 viability % Total CD45 cells/μL CD45 viability % |
| Kit components | CD34-PE/CD45-PerCP/Sytox Blue reagent Calibration bead solution Ammonium chloride lysing solution ADAMII Assay Slides | • CD45 FITC/CD34 PE reagent • 7-aminoactinomycin-D (7-AAD) reagent • Ammonium chloride lysing solution • BD Trucount tubes |
| Measuring range | CD34+ cells: 1 – 1,000 cells/μL | For FACSLyric flow cytometer: CD34+ cells: 1 – 1,000 cells/μL For FACSCalibur flow cytometer: CD34+ cells: 0 – 1,000 cells/μL |
| Measuring time | ~ 7 min/test | |
| Sample volume | MPB: 20 μL HPC-A: 20 μL Cord blood (FCB, TFCB): 50 μL | 100 μL |
| Measuring volume | ~ 8 μL | Not reported |
| Sample stability | • Mobilized Peripheral Blood: Stain specimens within 24 hours of collection • Fresh Leukapheresis Products: Stain specimens within 24 hours of collection • Fresh Cord Blood: Stain specimens within 48 hours of collection • Thawed Cord Blood: Stain immediately after thawing | • Normal Peripheral Blood: Stain specimens within 24 hours of collection • Mobilized Peripheral Blood: Stain specimens within 24 hours of collection • Fresh Leukapheresis Products: Stain specimens within 24 hours of collection • Fresh Cord Blood: Stain specimens within 48 hours of collection • Fresh Bone Marrow: Stain specimens within 24 hours of collection • Thawed Leukapheresis Products: Stain immediately after thawing • Thawed Cord Blood: Stain immediately after thawing • Thawed Bone Marrow: Stain immediately after thawing |
| Stain sample stability | • Mobilized Peripheral Blood: Keep prepared samples on wet ice and measure within 1 hour of lysing • Fresh Leukapheresis Products: Keep prepared samples on wet ice and measure within 1 hour of lysing • Fresh Cord Blood: Keep prepared samples on wet ice and measure within 1 hour of lysing • Thawed Cord Blood: Measure immediately post-lysis | • Fresh Leukapheresis Products: Acquire within 1 hour of lysing • Mobilized Peripheral Blood: Acquire within 1 hour of lysing • Fresh Cord Blood: Acquire within 1 hour of lysing • Thawed Cord Blood: Acquire immediately post-lysis |
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| Interfering conditions | No interference was observed in samples with up to 7.5 mg/dL of albumin. No interference was observed in samples with up to 10 mg/dL of bilirubin. No interference was observed in samples with up to 550 µg/mL of cyclophosphamide. No interference was observed in samples with up to 50 mg/dL of hemoglobin. No interference was observed in samples with up to 0.25 µg/mL of doxorubicin. No interference was observed in samples with up to 60 ng/mL of G-CSF. No interference was observed in samples with up to 250 mg/dL of intralipid. No interference was observed in samples with up to 20 µg/mL of paclitaxel. No interference was observed in samples with up to 1% of gamma-globulin. | No interference was observed in samples with up to 60 mg/mL of albumin. No interference was observed in samples with up to 40 mg/dL of bilirubin. No interference was observed in samples with up to 550 µg/mL of cyclophosphamide. No interference was observed in samples with up to 1 g/dL of hemoglobin. No interference was observed in samples with up to 1.932 µg/mL of doxorubicin. No interference was observed in samples with up to 60 ng/mL of G-CSF. No interference was observed in samples with up to 1,140 mg/dL of intralipid. No interference was observed in samples with up to 10.8µg/mL of paclitaxel. |
| --- | --- | --- |
**Table 3 Instruments**
| | ADAMII | BD FACSCalibur™ | BD FACSLyric™ |
| --- | --- | --- | --- |
| **Light Source** | Green LED (525nm) Blue LED (488nm) | Blue laser (488 nm) Red laser (635 nm) | Blue laser: 488 nm, 20 mw Red laser: 640 nm, 40 mw Violet laser: 405 nm, 40 mw |
| **Fluorescence filters** | FITC Ex 466/40, Em 525/50 PE Ex 510/42, Em 572/28 PerCP Ex 525/50, Em 650LP | FL1 530/30 FL2 585/42 FL3 670LP FL4 661/16 | FITC 527/32 PE 586/42 PerCP 700/54 PE-Cy7 783/56 APC 660/10 APC-Cy7 783/56 |
| **Method of Detection** | High-sensitivity monochrome CCD | Photodiode and PMT | Photodiode and PMT |
| **Objective Lens** | 10X objective and 0.7X tube lens | Specification not available | Flow cell lens: 1.2 NA |
| **Stage** | Automated X-Y-Z stage | Manual, Automated universal loader (optional) | Manual, Automated universal loader (optional) |
| **Exported formats: Image** | JPEG | N/A | N/A |
| **Electronic input** | 12V DC, 5.0A | 20 A, 1,725 W | 2 A, 200 W |
| **Operating Power** | 100 – 240 VAC, 1.5 A 50/60 Hz | 120 V ± 10% VAC 50 – 60 ± 2 Hz | 100 – 240 V ± 10% VAC 50 – 60 ± 10% Hz |
| **Operating environment** | 5 – 40°C, 20 -95% | 16 -29°C, 10 -90% | 15 - 30°C, 15 – 85% |
| **Weight** | 19.3 kg | ~ 109 kg | ~ 70 kg |
| **Dimensions** | 30W x 42D x 37H cm | 91W x 61D x 67H cm | 107W x 58D x 58H cm |
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# H. Summary of Performance Data:
# 1. Summary of Method Comparison/Accuracy
| ADAMII-CD34 kit compared to BD Stem Cell Enumeration Kit Pooled Data | | | | | |
| --- | --- | --- | --- | --- | --- |
| Parameters | N | Absolute Difference | | Relative Difference to Predicate (%) | |
| | | Mean Absolute Bias | 95% CI | Mean Relative Bias | 95% CI |
| CD34 (cells/μL) | 913 | 0.68 | -0.96 to 2.32 | 0.81 | 0.17% to 1.46% |
| %CD34 in CD45 | 913 | 0.0001 | -0.002 to 0.004 | 0.43 | -0.30% to 1.16% |
| CD45 (1000 cells/μL) | 913 | -0.83 | -1.26 to -0.40 | 0.36 | -0.15% to -0.87% |
| ADAMII-CD34 Kit Regression Analysis | | | | |
| --- | --- | --- | --- | --- |
| Parameter | N | R² | Slope (95% CI) | Intercept (95% CI) |
| Pooled data | | | | |
| CD34 (cells/μL) | 913 | 0.99 | 1.00 1.00 - 1.00 | 0.05 -0.19 - 0.34 |
| %CD34 in CD45 | 913 | 0.98 | 1.00 1.00 - 1.01 | 0.00 -0.002 - 0.00 |
| CD45 (1000 cells/μL) | 913 | 0.99 | 0.99 0.99 - 1.00 | 0.15 0.06 - 0.25 |
| Fresh and frozen cord blood | | | | |
| CD34 (cells/μL) | 283 | 0.99 | 0.99 (0.98 - 1.00) | 0.07 (-0.31 - 0.50) |
| % CD34 in CD45 | 283 | 0.97 | 1.02 (1.00 - 1.04) | -0.01 (-0.02 - 0.01) |
| CD45 (1000 cells/ μL) | 283 | 0.96 | 0.99 (0.97 - 1.01) | 19.33 (-90.16 - 153.08) |
# 2. Summary of Precision
| | Clinical samples, CV [%] | | | | |
| --- | --- | --- | --- | --- | --- |
| | | | Site1 | Site2 | Site3 |
| Fresh cord blood | Viable CD34 | Low | 21.77 | 21.07 | 22.82 |
| | | Mid1 | 17.36 | 19.81 | 18.48 |
| | | Mid2 | 17.46 | 11.86 | 15.23 |
| | | High | 14.96 | 13.23 | 11.10 |
| | Viable CD45 | Low | 2.96 | 2.64 | 5.22 |
| | | Mid1 | 7.21 | 5.55 | 4.35 |
| | | Mid2 | 4.75 | 3.78 | 6.28 |
| | | High | 4.27 | 3.26 | 10.61 |
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| Thawed frozen cord blood | Viable CD34 | Low | 20.43 | 16.24 | 12.49 |
| --- | --- | --- | --- | --- | --- |
| | | Mid1 | 12.53 | 10.07 | 8.65 |
| | | Mid2 | 11.27 | 10.16 | 10.73 |
| | | High | 8.63 | 8.23 | 9.06 |
| | Viable CD45 | Low | 11.37 | 10.47 | 10.55 |
| | | Mid1 | 10.84 | 10.73 | 11.12 |
| | | Mid2 | 7.59 | 6.95 | 12.56 |
| | | High | 10.68 | 8.59 | 2.43 |
### 3. Summary of Linearity
- Previously, with MPB and HPC-A, we have established following linearities.
- CD34
- MPB: 1 ~ 100 cells/μL
- HPC-A: 1 ~ 1,000 cells/μL
- CD45
- 2,500 ~ 50,000 cells/μL
- In this application, we have established
- CD34
- Cord blood: 1 ~ 120 cells/μL
### 4. Summary of Sample Stability
For fresh cord blood samples, the age of stored sample and the age of stained sample are 48 hours and 1 hour, respectively.
For thawed frozen cord blood samples, the age of stored sample and the age of stained sample are immediately after thawing and lysing, respectively.
## J. Proposed Labeling
The labeling complies with 21 CFR §809.10. Symbols used in labeling comply with ISO 15223- 1:2016 Medical Devices – Symbols to be used with medical device labels, labelling and information to be supplied – Part 1: General requirements.
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## **K. Compliance with standards and guidelines**
Testing complied with the following guidelines except where modifications were required by FDA:
- • EN 61010-1:2010 (ed 3) Safety Requirements for Electrical Equipment for Measurement, Control, and Laboratory Use - Part 1: General Requirements
- • EN 61010-2-081:2001 (ed 1) +A1:2003 Safety requirements for electrical equipment for measurement, control and laboratory use - Part 2-081: Particular requirements for automatic and semi-automatic laboratory equipment for analysis and other purposes
- • EN 61010-2-101:2002 (ed 1) Safety requirements for electrical equipment for measurement, control and laboratory use - Part 2-101: Particular requirements for in vitro diagnostic (IVD) medical equipment
- • EN 61326-1:2013 Electrical equipment for measurement, control and laboratory use. EMC requirements. General requirements
- • EN 61326-2-6:2013 Electrical equipment for measurement, control and laboratory use – EMC requirements – Part 2-6: Particular requirements – In vitro diagnostic (IVD) medical equipment
- • CLSI EP05-A3, Evaluation of Precision Performance of Quantitative Measurement Methods
- • CLSI EP06-A, Evaluation of the Linearity of Quantitative Measurement Procedures; A Statistical Approach; Approved Guideline
- • CLSI EP17-A2, Evaluation of Detection Capability for Clinical Laboratory Measurement Procedures; Approved Guideline
- • CLSI EP25-A, Evaluation of Stability of In Vitro Diagnostic Reagents; Approved Guidelines
- • CLSI EP09-A3, Method Comparison and Bias Estimation Using Patient Samples; Approved Guideline (*withdrawn but current at time of testing*)
## **L. Conclusion**
The submitted information in this premarket notification is complete and supports a substantial equivalence determination when compared to the predicate device.
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