(448 days)
Not Found
No
The device description outlines a standard flow cytometry assay with a two-step procedure and analysis. There is no mention of AI, ML, or any algorithms beyond basic cell counting and calculation. The performance studies focus on analytical and clinical validation metrics typical for such assays, not on the performance of an AI/ML model.
No.
This device is an in-vitro diagnostic assay used for the identification and enumeration of specific T cells, which aids in assessing CMV-specific immune status and risk of CMV reactivation. It is not used to treat or prevent a disease or condition.
Yes
The kit is intended for "assessment of CMV-specific immune status and risk of CMV reactivation" and "used in conjunction with other laboratory and clinical findings," which are diagnostic purposes. While it cannot measure CMV infection or disease directly, it provides information crucial for diagnosis and risk stratification.
No
The device is a kit containing physical reagents (Dextramers and antibodies) used in a laboratory procedure (flow cytometry) to analyze blood samples. It is not solely software.
Based on the provided information, the Dextramer® CMV Kit is an IVD (In Vitro Diagnostic).
Here's why:
- Intended Use: The intended use explicitly states that it is a "semi-quantitative assay intended for the identification and enumeration of cytomegalovirus (CMV)-specific CD8+ T cells in anticoagulated (Na Heparin) whole blood specimens by flow cytometry." This describes a test performed in vitro (outside the body) on a biological specimen (whole blood) to provide information about a patient's health status (CMV-specific immune status and risk of CMV reactivation).
- Device Description: The description details a procedure involving the analysis of blood samples using reagents (Dextramers, antibodies) and a specific instrument (flow cytometer). This is characteristic of an in vitro diagnostic test.
- Anatomical Site: The test is performed on "Whole blood specimens," which is a biological sample taken from the body for in vitro analysis.
- Clinical Studies: The inclusion of clinical studies evaluating the kit's performance in assessing the risk of CMV reactivation in patients further supports its classification as an IVD, as IVDs are used to aid in clinical decision-making.
- Predicate Device: The mention of a predicate device (iTAg MHC Tetramer CMV Kit, K051122) which is also an IVD, suggests that this type of assay is typically regulated as an IVD.
The information clearly indicates that this device is designed to be used in vitro to diagnose or provide information about a patient's health condition.
N/A
Intended Use / Indications for Use
Dextramer® CMV Kit is a semi-quantitative assay intended for the identification and enumeration of cytomegalovirus (CMV)-specific CD8+ T cells in anticoagulated (Na Heparin) whole blood specimens by flow cytometry.
Dextramer® CMV Kit is indicated for assessment of CMV-specific immune status and risk of CMV reactivation in adult human stem cell transplant patients following immunosuppression and used in conjunction with other laboratory and clinical findings.
The kit cannot be used to measure CMV infection or disease.
The kit is limited to individuals with the following HLA types: A0101, A0201, B0702, B0801, B*3501.
Special instrument requirements:
FACSCanto II flow cytometer (Becton Dickinson).
Product codes (comma separated list FDA assigned to the subject device)
GKZ
Device Description
The Dextramer® CMV Kit comprises 5 CMV Dextramers, Negative control as well as 3 antibodies recognizing CD3, CD4, and CD8:
Dextramer reagents
- HLA-A*0101 / VTEHDTLLY / PE
- HLA-A*0201 / NLVPMVATV / PE
- HLA-B*0702 / TPRVTGGGAM / PE
- HLA-B*0801 / ELRRKMMYM / PE
- HLA-B*3501 / IPSINVHHY / PE
- Negative control / PE
Antibodies
- Anti-CD8/FITC
- Anti-CD3/PerCP
- Anti-CD4/PE
The Dextramer® CMV Kit accurately enumerates CMV-specific T cells in blood samples. This involves a two-step procedure followed by analysis by flow cytometry:
Step 1: Determination of the percentage of CMV-specific CD3CD8 T cells in the sample (Tube A)
Step 2: Determination of the absolute number of CD3CD8 T-cells in the sample (Tube C)
The absolute number of CMV-specific CD3CD8 T cells/ul blood is then determined.
Mentions image processing
Not Found
Mentions AI, DNN, or ML
Not Found
Input Imaging Modality
Not Found
Anatomical Site
Not Found
Indicated Patient Age Range
Adult
Intended User / Care Setting
Not Found
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)
Non-clinical studies:
- Analytical sensitivity: The functional assay sensitivity is 1 cells/ul as determined by the lowest concentration of cells (cells/ul) that can be determined with a CV% below 20%.
- Analytical specificity: 100% (35/35) routine blood specimens from CMV seronegative stem cell transplant recipients showed 0.00 - 0.06 cells/ul and thus below the functional assay sensitivity of 1 cell/ul.
- Inter-lab reproducibility: The inter-lab reproducibility CV ranged between 6% and 18%.
- Intra-lab reproducibility: The intra-lab reproducibility CV ranged between 5% and 14%.
- Linearity - Recovery: The Dextramer CMV assay showed linearity in the range of 1-107 CMV-specific T cells/ul with a slope ranging from 0.98-1.08. Recovery was 73-134%.
- Interference: There was no significant interference from the tested cell populations equivalent to 2x normal level for monocytes, equivalent to 3x normal level for granulocytes, equivalent to 3x normal level for platelets, and equivalent to 2x normal level for red blood cells.
- Cross-reaction: No significant cross-reaction with allele mismatching CMV Dextramer reagents. All results from analysis of 4 blood samples with CMV-specific T cells with HLA mis-matched CMV Dextramer were within 0.00 - 0.11 cells/ul and thus below the functional assay sensitivity of 1 cell/ul.
- Comparison with predicate: Analysis of blood specimens from stem cell transplant recipients representing 5 alleles for a total of 117 MHC multimer measurements using iTAq MHC Tetramer CMV Kit and Dextramer CMV Kit showed substantial equivalence based on Deming regression for enumeration of the subset of CD8+ T-cells and CMV-specific T-cells.
- CD8+ T-cells: Slope = 0.984 (95% CI: 0.92 to 1.05), Intercept = -0.4406 (95% CI: -8.47 to 7.59), r = 0.905
- CMV-specific T-cells: Slope = 1.010 (95% CI: 0.89 to 1.13), Intercept = 0.39 (95% CI: 0.09 to 0.69), r = 0.952
Clinical studies:
- Prospective study: 120 allogeneic SCT patients followed for up to one year.
- Results: Dextramer results were evaluated at Day 30, 100, and Day 365 post-transplant. Only day 100 shows significant association between CMV-specific CD8+ T cells status (=7 cells/uL): 3.4 (95% CI: 1.57 – 7.46)
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.
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.”
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Image /page/0/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo features a stylized representation of a human figure, composed of three overlapping profiles facing to the right. The profiles are rendered in a dark color, creating a sense of depth and unity. The text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" is arranged in a circular pattern around the figure.
Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002
March 2, 2017
Immudex Aps Liselotte Brix Chief Operating Officer Fruebjergvej 3 Copenhagen, DK 2100
Re: K153538
Trade/Device Name: Dextramer CMV Kit Regulation Number: 21 CFR 864.5220 Regulation Name: Automated differential cell counter Regulatory Class: II Product Code: GKZ Dated: February 22, 2017 Received: February 24, 2017
Dear Dr. Brix:
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 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.
1
If you 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/Resourcesfor You/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,
Kelly Oliner -S
FOR
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
2
DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration
Indications for Use
Form Approved: OMB No. 0910-0120 Expiration Date: January 31, 2017 See PRA Statement below.
510(k) Number (if known) K153538
Device Name
Dextramer® CMV Kit
Indications for Use (Describe)
Dextramer® CMV Kit is a semi-quantitative assay intended for the identification and enumeration of cytomegalovirus (CMV)-specific CD8+ T cells in anticoagulated (Na Heparin) whole blood specimens by flow cytometry.
Dextramer® CMV Kit is indicated for assessment of CMV-specific immune status and risk of CMV reactivation in adult human stem cell transplant patients following immunosuppression and used in conjunction with other laboratory and clinical findings.
The kit cannot be used to measure CMV infection or disease.
The kit is limited to individuals with the following HLA types: A0101, A0201, B0702, B3501.
Special instrument requirements:
FACSCanto II flow cytometer (Becton Dickinson).
Type of Use (Select one or both, as applicable)
区 Prescription Use (Part 21 CFR 801 Subpart D)
Over-The-Counter Use (21 CFR 801 Subpart C)
CONTINUE ON A SEPARATE PAGE IF NEEDED.
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DO NOT SEND YOUR COMPLETED FORM TO THE PRA STAFF EMAIL ADDRESS BELOW.
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FORM FDA 3881 (8/14)
Page 1 of 1
PSC Publishing Services (301) 443-6740
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D. 510(k) Summary
Image /page/3/Picture/1 description: The image shows the logo for "Immudex", a company focused on immunology. The word "Immudex" is written in a bold, sans-serif font, with the first two letters in orange and the rest in blue. Below the company name is the tagline "Immunology Taken to a Higher Level", written in a smaller, sans-serif font.
1. Applicant:
Immudex ApS Fruebjergvej 3 DK-2100 København Ø DENMARK
2. Contact Person:
Liselotte Brix Phone: +45 39179772 / +45 40910121 E-mail: lb@immudex.com
3. Summary Preparation Date:
February 28, 2017
4. Device Name and Classification:
Trade Name (proprietary name): Dextramer® CMV Kit
Common Name (usual name): None
Classification: Class II
Product code: GKZ, Counter, differential cell
Panel: Hematology
Regulation section: 21 CFR § 864.5220, Automated differential cell counter
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5. Substantial Equivalence Information:
Predicate name(s) and predicate 510(k) number(s):
| Predicate Device Name(s) | Manufacturer | 510(k) number(s) |
|---|---|---|
| iTAg MHC Tetramer CMV Kit | Beckman Coulter | K051122 |
Comparison with Predicate:
| Device | Predicate | |
|---|---|---|
| Name | Dextramer® CMV Kit | iTAg MHC Tetramer CMV Kit |
| Intended Use | Identification and enumeration of | |
| cytomegalovirus (CMV)-specific | ||
| CD8+ T cells in anticoagulated | ||
| venous whole blood | ||
| in adult human stem cell transplant | ||
| patients by flow cytometry. | Same | |
| Kit | ||
| components | ||
| & | ||
| Accessory | ||
| Reagents | Anti-CD8/FITC | |
| Anti-CD4/PE | ||
| Anti-CD3/PerCP | ||
| Dextramer CMV Set of 5 individual | ||
| MHC Dextramers labeled with PE. | ||
| FACS Lysing Solution | Anti-CD8/FITC | |
| Anti-CD4/PE | ||
| Anti-CD3/PC5 | ||
| CMV Tetramer Set of 5 individual | ||
| MHC Tetramers labeled with PE. | ||
| iTAg Lyse Reagent | ||
| Instrument | TruCount | |
| Flow cytometer | Flow-Count™ Fluorospheres | |
| Sample type | Whole blood | Same |
| Anti- | ||
| coagulant | Heparin | EDTA |
| Cell type | ||
| detected | CMV-specific CD8 + T cells | |
| Human T lymphocytes (CD3+), | ||
| suppressor/cytotoxic (CD3+CD8+) | ||
| T-lymphocyte subsets, and | ||
| helper/inducer (CD3+CD4+) T- | ||
| lymphocyte subsets | Same | |
| Detection | ||
| method | Multimers of MHC molecules | |
| displaying CMV-specific peptide | ||
| Antibodies bound to CD3, CD4 and | ||
| CD8 | Same | |
| MHC | ||
| Multimer | ||
| backbone | Dextran | Streptavidin |
| HLA types | ||
| (peptide | ||
| sequence) | HLA-A*0101 (VTEHDTLLY) | |
| HLA-A*0201 (NLVPMVATV) | Same | |
| Same | ||
| HLA-B*0702 (TPRVTGGGAM) | Same |
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| Controls | HLA-B0801 (ELRRKMMYM)
Same |
|--------------------------------------------|--------------------------------|
| | HLA-B3501 (IPSINVHHY)
Same |
| | Negative control
Similar |
| Negative control above
Same | |
| Control cells
IMMUNO-TROL Control Cells | |
6. Device Description:
The Dextramer® CMV Kit comprises 5 CMV Dextramers, Negative control as well as 3 antibodies recognizing CD3, CD4, and CD8:
Dextramer reagents
| HLA-A*0101 / VTEHDTLLY / PE | 25 tests/0.25 ml | Cat. No. CA2131-PE |
|---|---|---|
| HLA-A*0201 / NLVPMVATV / PE | 50 tests/0.50 ml | Cat. No. CB2132-PE |
| HLA-B*0702 / TPRVTGGGAM / PE | 25 tests/0.25 ml | Cat. No. CH2136-PE |
| HLA-B*0801 / ELRRKMMYM / PE | 25 tests/0.25 ml | Cat. No. CI2137-PE |
| HLA-B*3501 / IPSINVHHY / PE | 25 tests/0.25 ml | Cat. No. CK2138-PE |
| Negative control / PE | 150 tests/1.50 ml | Cat. No. CI3233-PE |
Antibodies
| Anti-CD8/FITC | 2 ml | Cat. No. A-CD8-FITC |
|---|---|---|
| Anti-CD3/PerCP | 2 ml | Cat. No. A-CD3-PerCP |
| Anti-CD4/PE | 2 ml | Cat. No. A-CD4-PE |
The Dextramer® CMV Kit accurately enumerates CMV-specific T cells in blood samples. This involves a two-step procedure followed by analysis by flow cytometry:
Step 1: Determination of the percentage of CMV-specific CD3CD8 T । cells in the sample (Tube A)
Step 2: Determination of the absolute number of CD3CD8 T-cells in the sample (Tube C)
The absolute number of CMV-specific CD3CD8 T cells/ul blood is then determined.
6
7. Intended use(s):
Dextramer® CMV Kit is a semi-quantitative assay intended for the identification and enumeration of cytomegalovirus (CMV)-specific CD8+ T cells in anticoagulated (Na Heparin) whole blood specimens by flow cytometry.
Dextramer® CMV Kit is indicated for assessment of CMV-specific immune status and risk of CMV reactivation in adult human stem cell transplant patients following immunosuppression and used in conjunction with other laboratory and clinical findings.
The kit cannot be used to measure CMV infection or disease.
The kit is limited to individuals with the following HLA types: A0101, A0201, B0702, B0801, B*3501.
Special instrument requirements:
FACSCanto II flow cytometer (Becton Dickinson).
8. Indication(s) for use:
Dextramer® CMV Kit is a semi-quantitative assay intended for the identification and enumeration of cytomegalovirus (CMV)-specific CD8+ T cells in anticoagulated (Na Heparin) whole blood specimens by flow cytometry.
Dextramer® CMV Kit is indicated for assessment of CMV-specific immune status and risk of CMV reactivation in adult human stem cell transplant patients following immunosuppression and used in conjunction with other laboratory and clinical findings.
The kit cannot be used to measure CMV infection or disease.
The kit is limited to individuals with the following HLA types: A0101, A0201, B0702, B0801, B*3501.
7
Special instrument requirements:
FACSCanto II flow cvtometer (Becton Dickinson).
9. Performance Characteristics:
Non-clinical studies
Analytical sensitivity
The functional assay sensitivity is 1 cells/ul as determined by the lowest concentration of cells (cells/ul) that can be determined with a CV% below 20%.
Analytical specificity
100% (35/35) routine blood specimens from CMV seronegative stem cell transplant recipients showed 0.00 - 0.06 cells/ul and thus below the functional assay sensitivity of 1 cell/ul.
Inter-lab reproducibility
The inter-lab reproducibility CV ranged between 6% and 18%.
Intra-lab reproducibility
The intra-lab reproducibility CV ranged between 5% and 14%.
Linearity - Recovery
The Dextramer CMV assay showed linearity in the range of 1-107 CMV-specific T cells/ul with a slope ranging from 0.98-1.08. Recovery was 73-134%.
Interference
There was no significant interference from the tested cell populations equivalent to 2x normal level for monocytes, equivalent to 3x normal level for granulocytes, equivalent to 3x normal level for platelets, and equivalent to 2x normal level for red blood cells.
Cross-reaction
No significant cross-reaction with allele mismatching CMV Dextramer reagents. All results from analysis of 4 blood samples with CMV-specific T cells with HLA mis-matched CMV Dextramer were within 0.00 - 0.11 cells/ul and thus below the functional assay sensitivity of 1 cell/ul.
Comparison with predicate
Analysis of blood specimens from stem cell transplant recipients representing 5 alleles for a total of 117 MHC multimer measurements using iTAq MHC Tetramer CMV Kit and Dextramer CMV Kit showed substantial equivalence based on
8
Deming regression for enumeration of the subset of CD8+ T-cells and CMVspecific T-cells.
| Slope | 95% CI | Intercept | 95% CI | r | |
|---|---|---|---|---|---|
| CD8+ T-cells | 0.984 | 0.92 to 1.05 | -0.4406 | -8.47 to 7.59 | 0.905 |
| CMV-specific T-cells | 1.010 | 0.89 to 1.13 | 0.39 | 0.09 to 0.69 | 0.952 |
Clinical studies
A prospective study with 120 allogeneic SCT patients followed for up to one year for recurrence of CMV infection and determination of numbers of CMV-specific CD8+ T cells using the CMV Dextramer Kit. Dextramer analysis were performed pre-transplant at day 30, 100 and 360 and included the alleles HLA-A0101, A0201, B0702, B0801 and B*3501.
68 patients were CMV seropositive (recipient and/or donor) prior to transplantation of which 34 patients developed antigenimia.
2x2 tables are provided for each time point posttransplant showing correlation of CMV-specific T-cell and occurance of CMV antigenimia and used for calculation of the risk of CMV infection/antigenimia after Day 100
Risk of developing CMV antigenemia after Day 100
Risk is defined as risk of patients with less than 7 cells/ul of developing CMV infection post Day 100 compared to patients with more than 7 cells/ul.
| Day 100 | Development of antigenemia (post Day 100) | ||
|---|---|---|---|
| # CMV+ T cells | Yes | No | Total |