(90 days)
No
The summary describes a flow cytometry system with reagents and analysis software (Kaluza C) for manual data analysis. There is no mention of automated classification, pattern recognition, or any other features typically associated with AI/ML in the context of flow cytometry data analysis. The interpretation is explicitly stated to be confirmed by a pathologist.
No
The device is described as an in vitro diagnostic (IVD) device used for qualitative identification of cell populations for differential diagnosis, not for treatment.
Yes
The "Intended Use / Indications for Use" section explicitly states that the ClearLLab 10C Panels "are intended for in vitro diagnostic use for qualitative identification of cell populations" and "These reagents are used as an aid in the differential diagnosis of hematologically abnormal patients." It further states that the Navios and Navios EX Flow Cytometers are "intended for use as an in vitro diagnostic device".
No
The device description clearly states that the system is comprised of various components including reagents, flow cytometers (hardware), compensation kits, control cells, and software (Kaluza C). While software is a component, it is not the sole component of the medical device system.
Yes, this device is an IVD (In Vitro Diagnostic).
Here's why:
- Explicit Statement: The "Intended Use / Indications for Use" section explicitly states: "The ClearLLab 10C Panels are intended for in vitro diagnostic use..." and "The Navios Flow Cytometer is intended for use as an in vitro diagnostic device..." and "The Navios EX Flow Cytometer is intended for use as an in vitro diagnostic device...".
- Purpose: The device is intended for "qualitative identification of cell populations by multiparameter immunophenotyping" using patient specimens (peripheral whole blood, bone marrow, and lymph node). This is a diagnostic process performed outside of the body.
- Clinical Application: The reagents are used "as an aid in the differential diagnosis of hematologically abnormal patients having, or suspected of having, the following hematopoietic neoplasms: chronic leukemia, non-Hodgkin lymphoma, myeloma, myeloma, myelodysplastic syndrome (MDS), and/or myeloproliferative neoplasms (MPN)." This directly relates to diagnosing diseases.
- Specimen Type: The device analyzes biological specimens (blood, bone marrow, lymph node) collected from the human body.
- Intended User: The results are intended to be interpreted by a "pathologist or equivalent professional in conjunction with other clinical and laboratory findings," indicating a clinical diagnostic setting.
- Predicate Devices: The listed predicate devices (DEN160047 ClearLLab Reagents, K130373 Navios Flow Cytometer, K162897 Navios EX Flow Cytometer) are also IVDs, which supports the classification of this device.
All of these points align with the definition of an In Vitro Diagnostic device.
N/A
Intended Use / Indications for Use
- ClearLLab 10C Panels (B, T, M1, M2): "The ClearLLab 10C Panels are intended for in vitro diagnostic use for qualitative identification of cell populations by multiparameter immunophenotyping on the Navios EX flow cytometers. These reagents are used as an aid in the differential diagnosis of hematologically abnormal patients having, or suspected of having, the following hematopoietic neoplasms: chronic leukemia, non-Hodgkin lymphoma, myeloma, myeloma, myelodysplastic syndrome (MDS), and/or myeloproliferative neoplasms (MPN). The reagents can be used with peripheral whole blood (collected in K2EDTA, Acid Citrate Dextrose (ACD) or Heparin), bone marrow (collected in K2EDTA, ACD or Heparin) and lymph node specimens. Interpretation of the results should be confirmed by a pathologist or equivalent professional in conjunction with other clinical and laboratory findings. These reagents provide multiparameter, qualitative results for the surface antigens listed below: ClearLLab 10C B Cell Tube: Kappa, Lambda, CD10, CD5, CD200, CD34, CD38, CD20, CD19, CD45; ClearLLab 10C T Cell Tube: TCRy8, CD4, CD2, CD56, CD5, CD34, CD3, CD8, CD7, CD45; ClearLLab 10C M1 Cell Tube: CD16, CD7, CD10, CD13, CD64, CD34, CD14, HLA-DR, CD11b, CD45; ClearLLab 10C M2 Cell Tube: CD15, CD123, CD117, CD13, CD34, CD38, HLA-DR, CD19, CD45"
- Navios Flow Cytometer: "The Navios Flow Cytometer is intended for use as an in vitro diagnostic device for immunophenotyping using up to ten fluorescent detection channels using three lasers (488 nm, and 405 nm) and two light scatter detection channels. It is intended for use with in vitro diagnostic (IVD) assays and software that are indicated for use with the instrument."
- Navios EX Flow Cytometer: "The Navios EX Flow Cytometer is intended for use as an in vitro diagnostic device for immunophenotyping using up to ten fluorescent detection channels using three lasers (488 nm, and 405 mm) and two light scatter detection channels. It is intended for use with in vitro diagnostic (IVD) assays and software that are indicated for use with the instrument."
Product codes (comma separated list FDA assigned to the subject device)
PWD, OYE
Device Description
"The new ClearLLab 10C reagent system is comprised of various components and is described below. Figures 2 and 3 illustrate the anticipated workflow from instrument setup through data analysis with a breakout of the standardization and Quality Control sequence for the new reagent system. As the figures show, the process is in-line with standard flow cytometry protocol. Four ClearLLab 10C Panels [B, T, M1 and M2]; Navios and Navios EX flow cytometers [3 laser/10 color configurations]; ClearLLab Compensation Kit; ClearLLab Compensation Beads; ClearLLab Control Cells, normal and abnormal; Kaluza C data analysis software; Flow-Check Pro Fluorospheres; Flow-Set Pro Fluorospheres; IOTest 3 Fixative Solution; IOTest 3 Lysing Solution. The ClearLLab 10C reagent system is run on Beckman Coulter's Navios or Navios EX flow cytometer (3 Laser/10 Color configurations). It requires off-line manual sample processing and use of the accompanying lysing reagent. As part of the ClearLLab 10C reagent system, to allow proper utilization of this application, the indications for the Navios and Navios EX flow cytometers include all ten fluorescent detection channels and three laser configurations (blue, red and violet). LMD data analysis is performed manually using the Kaluza C Analysis Software. This Analysis Software package is supplied separately from the Navios EX system softwares and must be installed on an independent computer workstation for off-line analysis of listmode files generated on the flow cytometer with the associated reagents and cytometer system software package, including Control Cell OC data and sample data analysis. The Navios and Navios EX analysis software are NOT be recommended for use with this application (Note that QC data from Flow-Set Pro, Flow-Check Pro, and Compensation products will continue to be analyzed using the on-board instrument software). Kaluza C Software is a software tool designed to work with *.Imd files generated from flow cytometers. Preset Kaluza C analysis templates for the ClearLLab 10c reagent system are provided."
Mentions image processing
Not Found
Mentions AI, DNN, or ML
Not Found
Input Imaging Modality
Not Found
Anatomical Site
peripheral whole blood, bone marrow, lymph node specimens
Indicated Patient Age Range
Not Found
Intended User / Care Setting
Pathologist or equivalent professional / 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)
- Laser Performance Characteristics:
- Study Type: Verify stability of the laser performance
- Sample Size: Not specified
- Key results: "Analysis of the data collected demonstrates that the Navios and Navios EX laser performance is stable over time."
- Instrument Carryover:
- Study Type: To verify carryover using Flow-Check Pro fluorospheres meets performance specifications.
- Sample Size: Not specified
- Key results: "Analysis of the data collected demonstrates that the Navios and Navios EX meet the carryover performance requirements."
- Instrument Linearity:
- Study Type: Verify fluorescence detection is linear
- Sample Size: Not specified
- Key results: "Linearity of fluorescence measurements was demonstrated."
- Navios vs. Navios EX Percent Cell Recovery Equivalence Study:
- Study Type: Demonstrate the equivalent performance in % cell recovery between Navios and Navios EX flow cytometers when running ClearLLab 10C application.
- Sample Size: Not specified
- Key results: "Analysis of the data collected demonstrates that the Navios and Navios EX Flow Cytometry Systems are equivalence when running the ClearLLab 10C application."
- Characterization (Antibody Specificity):
- Study Type: Demonstrate antibody specificity including Fluorescence Minus One
- Sample Size: Not specified
- Key results: "Analysis of the data collected demonstrates that specific antibody clones and polyclonal antibody reagents are identified for ClearLLab 10C reagent panel markers."
- Characterization (Optimal Reagent Dosage):
- Study Type: Titrate for optimal reagent dosage
- Sample Size: Not specified
- Key results: "Analysis of the data collected demonstrates that antibody conjugates dosing values are determined for was defined for each antibody of ClearLLab 10C reagents."
- Characterization (Non-Specific Binding):
- Study Type: Assess of Non-Specific Binding
- Sample Size: Not specified
- Key results: "Analysis of the data collected demonstrates solutions implemented to reduce and/or obtain acceptable level of non-specific binding."
- Lot-to-Lot Reproducibility (ClearLLab 10C Panels):
- Study Type: Demonstrate variability of multiple lots of material.
- Sample Size: Not specified
- Key results: "Analysis of the data collected demonstrates that the ClearLLab 10C panels have acceptable lot variability performance."
- Stability (ClearLLab 10C Panels):
- Study Type: Demonstrate reagent stability.
- Sample Size: Not specified
- Key results: "Analysis of the data collected demonstrates that the ClearLLab 10C panels met performance requirements in support of the product's stability claims."
- Carryover - Specimen and Reagent:
- Study Type: To verify carryover of specimen and reagents on the Navios and Navios EX meets performance specifications.
- Sample Size: Not specified
- Key results: "Analysis of the data collected demonstrates that the Navios and Navios EX meets carryover performance requirements."
- Bulk vs. Single Wash:
- Study Type: Demonstrate equivalency of sample preparation methods.
- Sample Size: Not specified
- Key results: "Equivalency of single tube wash and bulk wash methodology was demonstrated."
- Detection Capability:
- Study Type: To verify that the ClearLLab 10C panels with the Navios or Navios EX meet the performance requirements for the ability to differentiate between abnormal and normal populations.
- Sample Size: Not specified
- Key results: "Analysis of the data collected demonstrates that the ClearLLab 10C panels with the Navios or Navios EX meet the performance requirements for Detection Capability."
- Specimen Age and Prepared Sample Stability (Whole Blood and Bone Marrow):
- Study Type: Verify whole blood and bone marrow specimen and prepared sample stability claims.
- Sample Size: Not specified
- Key results: "Analysis of the data collected demonstrates that the ClearLLab 10C panels meet the requirements for specimen and prepared sample stability (Whole Blood and Bone Marrow)."
- Specimen Age and Prepared Sample Stability (Lymph Node):
- Study Type: Verify lymph node samples prepared sample stability claim.
- Sample Size: Not specified
- Key results: "Analysis of the data collected demonstrates that the ClearLLab 10C panels meet the requirements for prepared sample stability (Lymph Node)."
- Anticoagulant Equivalency – Whole Blood:
- Study Type: Demonstrate equivalent performance of whole blood specimens collected in several different anticoagulants (K2EDTA, Heparin and ACD) on the Navios system using ClearLLab 10C panels.
- Sample Size: Not specified
- Key results: "Performance of ClearLLab 10C panels with whole blood specimens collected in K2EDTA, Heparin and ACD anticoagulants was demonstrated to be equivalent."
- Anticoagulant Method Comparison - 10C to 5C:
- Study Type: Demonstrate equivalency of anticoagulants used with bone marrow and whole blood specimens with the ClearLLab 10C panels in reference to the ClearLLab 5 color reagents.
- Sample Size: Not specified
- Key results: "For all conditions evaluated, the data collected demonstrates that the various anticoagulants are equivalent."
- Precision - Control Material:
- Study Type: Demonstrate system imprecision using control material as a surrogate for a stabilized sample
- Sample Size: Not specified
- Key results: "Analysis of the data collected demonstrates that the ClearLLab 10C panels meet performance requirements for repeatability and reproducibility."
- Precision - Multi-Site with Clinical Specimens:
- Study Type: Demonstrate assay repeatability and reproducibility using both normal and clinical specimens.
- Sample Size: Not specified
- Key results: "Analysis of the data collected demonstrates that the ClearLLab 10C panels meet performance requirements for repeatability and reproducibility."
- Precision - Operator and Instrument Variability:
- Study Type: Demonstrate system imprecision performance of the ClearLLab 10C panels using the same specimen prepared by three (3) operators, twice a day, on two (2) Navios EX flow cytometers.
- Sample Size: Not specified
- Key results: "The ClearLLab 10C panels when run on each specimen type by different operators on different Navios EX flow cytometers demonstrated acceptable precision performance and met acceptance criteria."
- Clinical Accuracy:
- Study Type: Evaluate the clinical accuracy of the ClearLLab 10C Panels in identifying an abnormal or normal phenotype vs. the site's clinical diagnosis of malignant or non-malignant outcome from the current standard of care
- Sample Size: Not specified
- Key results: "Analysis of the data collected demonstrates that the ClearLLab 10C panels are able identify the abnormal population when compared to clinical outcome."
- IOTest 3 Fixative and IOTest 3 Lysing Solution - Lot-to-Lot Reproducibility:
- Study Type: Demonstrate variability of multiple lots of material.
- Sample Size: Not specified
- Key results: "Analysis of the data collected demonstrates that the IOTest 3 Fixative and Lysing Solutions have acceptable lot variability performance."
- Flow-Set Pro Lot-to-Lot Variability:
- Study Type: Demonstrate variability of multiple lots of material.
- Sample Size: Not specified
- Key results: "Analysis of the data collected demonstrates that the Flow-Set Pro have acceptable lot variability performance."
- Flow-Check Pro Lot-to-Lot Variability:
- Study Type: Demonstrate variability of multiple lots of material.
- Sample Size: Not specified
- Key results: "Analysis of the data collected demonstrates that the Flow-Check Pro have acceptable lot variability performance."
- ClearLLab Compensation Kit with ClearLLab Compensation Beads Reagent Stability:
- Study Type: Demonstrate reagent stability.
- Sample Size: Not specified
- Key results: "Analysis of the data collected demonstrates that the Compensation Kit and Compensation Beads meet performance requirements in support of the products' stability claims."
- IOTest 3 Lysing Solution and Fixative Reagent Stability:
- Study Type: Demonstrate reagent stability.
- Sample Size: Not specified
- Key results: "Analysis of the data collected demonstrates that the IOTest 3 Fixative Solution and Lysing Solutions meet performance requirements in support of the product's stability claims."
- Flow-Set Pro Fluorospheres Reagent Stability:
- Study Type: Demonstrate reagent stability.
- Sample Size: Not specified
- Key results: "Analysis of the data collected demonstrates that the Flow-Set Pro Fluorospheres meet performance requirements in support of the product's stability claims."
- Flow-Check Pro Fluorospheres Reagent Stability:
- Study Type: Demonstrate reagent stability.
- Sample Size: Not specified
- Key results: "Analysis of the data collected demonstrates that the Flow-Check Pro Fluorospheres meet performance requirements in support of the product's stability claims."
- Flow-Set Pro Analyte Value Assignment:
- Study Type: Define Flow-Set Pro Target ranges for use with the ClearLLab 10C panels and define a process for ranges transfer from one lot of Flow-Set Pro Fluorospheres.
- Sample Size: Not specified
- Key results: "Analysis of the data collected demonstrates that appropriate Flow-Set Pro target ranges are defined for use with the ClearLLab 10C panels and that a process for ranges transfer from one lot of Flow-Set Pro Fluorospheres to another one is in place."
Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)
Not Found
Predicate Device(s): If the device was cleared using the 510(k) pathway, identify the Predicate Device(s) K/DEN number used to claim substantial equivalence and list them here in a comma separated list exactly as they appear in the text. List the primary predicate first in the list.
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
§ 864.7010 Flow cytometric test system for hematopoietic neoplasms.
(a)
Identification. A flow cytometric test for hematopoietic neoplasms is a device that consists of reagents for immunophenotyping of human cells in relation to the level of expression, antigen density, and distribution of specific cellular markers. These reagents are used as an aid in the differential diagnosis or monitoring of hematologically abnormal patients having or suspected of having hematopoietic neoplasms. The results should be interpreted by a pathologist or equivalent professional in conjunction with other clinical and laboratory findings.(b)
Classification. Class II (special controls). The special controls for this device are:(1) Premarket notification submissions must include the following information:
(i) The indications for use must indicate the clinical hematopoietic neoplasms for which the assay was designed and validated, for example, chronic leukemia or lymphoma.
(ii) A detailed device description including the following:
(A) A detailed description of all test components, all required reagents, and all instrumentation and equipment, including illustrations or photographs of nonstandard equipment or methods.
(B) Detailed documentation of the device software including, but not limited to, standalone software applications and hardware-based devices that incorporate software.
(C) A detailed description of methodology and assay procedure.
(D) A description of appropriate internal and external quality control materials that are recommended or provided. The description must identify those control elements that are incorporated into the testing procedure, if applicable.
(E) Detailed specifications for sample collection, processing, and storage.
(F) Detailed specification of the criteria for test results interpretation and reporting including pre-established templates.
(G) If applicable, based on the output of the results, a description of the specific number of events to collect, result outputs, and analytical sensitivity of the assay that will be reported.
(iii) Information that demonstrates the performance characteristics of the test, including:
(A) Device performance data from either a method comparison study comparing the specific lymphocyte cell markers to a predicate device or data collected through a clinical study demonstrating clinical validity using well-characterized clinical specimens. Samples must be representative of the intended use population of the device including hematologic neoplasms and the specific sample types for which the test is indicated for use.
(B) If applicable, device performance data from a clinical study demonstrating clinical validity for parameters not established in a predicate device of this generic type using well-characterized prospectively obtained clinical specimens including all hematologic neoplasms and the specific sample types for which the device is indicated for use.
(C) Device precision data using clinical samples to evaluate the within-lot, between-lot, within-run, between run, site-to-site and total variation using a minimum of three sites, of which at least two sites must be external sites. Results shall be reported as the standard deviation and percentage coefficient of variation for each level tested.
(D) Reproducibility data generated using a minimum of three lots of reagents to evaluate mean fluorescence intensity and variability of the recovery of the different markers and/or cell populations.
(E) Data from specimen and reagent carryover testing performed using well-established methods (
e.g., CLSI H26-A2).(F) Specimen and prepared sample stability data established for each specimen matrix in the anticoagulant combinations and storage/use conditions that will be indicated.
(G) A study testing anticoagulant equivalency in all claimed specimen type/anticoagulant combinations using clinical specimens that are representative of the intended use population of the device.
(H) Analytic sensitivity data using a dilution panel created from clinical samples.
(I) Analytical specificity data, including interference and cross-contamination.
(J) Device stability data, including real-time stability of reagents under various storage times and temperatures.
(K) For devices that include polyclonal antibodies, Fluorescence Minus One (FMO) studies to evaluate non-specific binding for all polyclonal antibodies. Each FMO tube is compared to reagent reference to demonstrate that no additional population appears when one marker is absent. Pre-specified acceptance criteria must be provided and followed.
(L) For devices indicated for use as a semi-quantitative test, linearity data using a dilution panel created from clinical samples.
(M) For devices indicated for use as a semi-quantitative test, clinically relevant analytical sensitivity data, including limit of blank, limit of detection, and limit of quantification.
(iv) Identification of risk mitigation elements used by the device, including a detailed description of all additional procedures, methods, and practices incorporated into the instructions for use that mitigate risks associated with testing the device.
(2) The 21 CFR 809.10 compliant labeling must include the following:
(i) The intended use statement in the 21 CFR 809.10(a)(2) and (b)(2) compliant labeling must include a statement that the results should be interpreted by a pathologist or equivalent professional in conjunction with other clinical and laboratory findings. The intended use statement must also include information on what the device detects and measures, whether the device is qualitative, semi-quantitative, and/or quantitative, the clinical indications for which the device is to be used, and the specific population(s) for which the device is intended.
(ii) A detailed description of the performance studies conducted to comply with paragraph (b)(1)(iii) of this section and a summary of the results.
(3) As part of the risk management activities performed under 21 CFR 820.30 design controls, product labeling and instruction manuals must include clear examples of all expected phenotypic patterns and gating strategies using well-defined clinical samples representative of both abnormal and normal cellular populations. These samples must be selected based upon the indications described in paragraph (b)(1)(i) of this section.
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Image /page/0/Picture/0 description: The image shows the logo of the U.S. Food and Drug Administration (FDA). On the left is the Department of Health & Human Services logo. To the right of that is the FDA logo, which is a blue square with the letters "FDA" in white. To the right of the blue square is the text "U.S. FOOD & DRUG ADMINISTRATION" in blue.
March 21, 2019
Beckman Coulter Anthony Dennis Sr. Manager 11800 SW 147th Ave. Miami, Florida 33196-2500
Re: K183592
Trade/Device Name: ClearLLab 10C Panels (B, T, M1, M2), Navios Flow Cytometer, Navios EX Flow Cytometer Regulation Number: 21 CFR 864.7010 Regulation Name: Flow cytometric test system for hematopoietic neoplasms Regulatory Class: Class II Product Code: PWD, OYE Dated: December 20, 2018 Received: December 21, 2018
Dear Anthony Dennis:
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 mav, therefore, market the device, subject to the general controls provisions of the Act. Although this letter refers to your product as a device, please be avare that some cleared products may instead be combination products. The 510(k) Premarket Notification Database located at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/pmn.cfm identifies combination product submissions. 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
1
requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Part 801 and Part 809); medical device reporting of medical device-related adverse events) (21 CFR 803) for devices or postmarketing safety reporting (21 CFR 4, Subpart B) for combination products (see https://www.fda.gov/CombinationProducts/GuidanceRegulatoryInformation/ucm597488.htm); good manufacturing practice requirements as set forth in the quality systems (OS) regulation (21 CFR Part 820) for devices or current good manufacturing practices (21 CFR 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.
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 comprehensive regulatory information about medical devices and radiation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/) and CDRH Learn (http://www.fda.gov/Training/CDRHLearn). Additionally, you may contact the Division of Industry and Consumer Education (DICE) to ask a question about a specific regulatory topic. See the DICE website (http://www.fda.gov/DICE) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).
Sincerely.
Douglas A. Jeffery -S
Doug Jeffery Acting Deputy 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) K183592
Device Name ClearLLab 10C Panels (B, T, M1, M2)
Indications for Use (Describe)
The ClearLLab 10C Panels are intended for in vitro diagnostic use for qualitative identification of cell populations by multiparameter immunophenotyping on the Navios EX flow cytometers. These reagents are used as an aid in the differential diagnosis of hematologically abnormal patients having, or suspected of having, the following hematopoietic neoplasms: chronic leukemia, non-Hodgkin lymphoma, myeloma, myeloma, myelodysplastic syndrome (MDS), and/or myeloproliferative neoplasms (MPN). The reagents can be used with peripheral whole blood (collected in K2EDTA, Acid Citrate Dextrose (ACD) or Heparin), bone marrow (collected in K2EDTA, ACD or Heparin) and lymph node specimens. Interpretation of the results should be confirmed by a pathologist or equivalent professional in conjunction with other clinical and laboratory findings.
These reagents provide multiparameter, qualitative results for the surface antigens listed below:
- · ClearLLab 10C B Cell Tube: Kappa, Lambda, CD10, CD5, CD200, CD34, CD38, CD20, CD19, CD45
- · ClearLLab 10C T Cell Tube: TCRy8, CD4, CD2, CD56, CD5, CD34, CD3, CD8, CD7, CD45
- ClearLLab 10C M1 Cell Tube: CD16, CD7, CD10, CD13, CD64, CD34, CD14, HLA-DR, CD11b, CD45
- ClearLLab 10C M2 Cell Tube: CD15, CD123, CD117, CD13, CD34, CD38, HLA-DR, CD19, CD45
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) K183592
Device Name Navios Flow Cytometer
Indications for Use (Describe)
The Navios Flow Cytometer is intended for use as an in vitro diagnostic device for immunophenotyping using up to ten fluorescent detection channels using three lasers (488 nm, and 405 nm) and two light scatter detection channels. It is intended for use with in vitro diagnostic (IVD) assays and software that are indicated for use with the instrument.
| 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."
4
Indications for Use
510(k) Number (if known) K183592
Device Name Navios EX Flow Cytometer
Indications for Use (Describe)
The Navios EX Flow Cytometer is intended for use as an in vitro diagnostic device for immunophenotyping using up to ten fluorescent detection channels using three lasers (488 nm, and 405 mm) and two light scatter detection channels. It is intended for use with in vitro diagnostic (IVD) assays and software that are indicated for use with the instrument.
| 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."
5
| Section 5 | 510(k) Summary |
|---|---|
| ----------- | ---------------- |
6
510(k) Summary for ClearLLab 10C Reagents
510(k) Owner / Submitter Information
Name: Beckman Coulter Inc. Address: 11800 SW 147th Ave., Miami, FL 33196 Phone #: (305) 380-4509 Fax #: (305) 380-4344 Contact Person: Anthony Dennis Email Address: adennis@beckman.com Date Submitted: 12 December 2018
Device Information
Trade Name: ClearLLab 10C (T), ClearLLab 10C (B), ClearLLab 10C (M1), ClearLLab (M2) Common Name: ClearLLab Reagents Classification Name: Flow Cytometric Test System for Hematopoietic Neoplasms (21 CFR 864.7010) Classification: Class II Product Code: PWD Panel: Hematology
Trade Name: Navios Flow Cvtometer
Common Name: Navios Flow Cytometer Classification Name: Automated differential cell counter (21 CFR 864.5220) Classification: Class II Product Code: OYE Panel: Hematology
Trade Name: Navios EX Flow Cytometer
Common Name: Navios EX Flow Cytometer Classification Name: Automated differential cell counter (21 CFR 864.5220) Classification: Class II Product Code: OYE Panel: Hematology
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Predicate Device Information
| Predicate Product | 510(k)
Number | Date
Cleared | Classification | 21 CFR | Product
Code |
|--------------------------|------------------|-----------------|----------------|----------|-----------------|
| ClearLLab Reagents | DEN160047 | 06/29/2017 | Class II | 864.7010 | PWD |
| Navios Flow Cytometer | K130373 | 9/18/2013 | Class II | 864.5220 | OYE |
| Navios EX Flow Cytometer | K162897 | 6/23/2017 | Class II | 864.5220 | OYE |
Device Description
The new ClearLLab 10C reagent system is comprised of various components and is described below. Figures 2 and 3 illustrate the anticipated workflow from instrument setup through data analysis with a breakout of the standardization and Quality Control sequence for the new reagent system. As the figures show, the process is in-line with standard flow cytometry protocol.
- Four ClearLLab 10C Panels [B, T, M1 and M2] A
-
Navios and Navios EX flow cytometers [3 laser/10 color configurations]
- ClearLLab Compensation Kit A
- ClearLLab Compensation Beads A
- ClearLLab Control Cells, normal and abnormal A
- A Kaluza C data analysis software
- Flow-Check Pro Fluorospheres A
- Flow-Set Pro Fluorospheres A
-
IOTest 3 Fixative Solution
-
IOTest 3 Lysing Solution
The ClearLLab 10C reagent system is run on Beckman Coulter's Navios or Navios EX flow cytometer (3 Laser/10 Color configurations). It requires off-line manual sample processing and use of the accompanying lysing reagent. As part of the ClearLLab 10C reagent system, to allow proper utilization of this application, the indications for the Navios and Navios EX flow cvtometers include all ten fluorescent detection channels and three laser configurations (blue, red and violet).
LMD data analysis is performed manually using the Kaluza C Analysis Software. This Analysis Software package is supplied separately from the Navios EX system softwares and must be installed on an independent computer workstation for off-line analysis of listmode files generated on the flow cytometer with the associated reagents and cytometer system software package, including Control Cell OC data and sample data analysis. The Navios and Navios EX analysis software are NOT be recommended for use with this application (Note that QC data from Flow-Set Pro, Flow-Check Pro, and Compensation products will continue to be analyzed using the on-board instrument software).
Kaluza C Software is a software tool designed to work with *.Imd files generated from flow cytometers.
8
Preset Kaluza C analysis templates for the ClearLLab 10c reagent system are provided.
Intended Use:
ClearLLab 10C Reagents
The ClearLLab 10C Panels are intended for in vitro diagnostic use for qualitative identification of cell populations by multiparameter immunophenotyping on the Navios and Navios EX flow cytometers. These reagents are used as an aid in the differential diagnosis of hematologically abnormal patients having, or suspected of having, the following hematopoietic neoplasms: chronic leukemia, acute leukemia, non-Hodgkin lymphoma, myeloma, myelodysplastic syndrome (MDS), and/or myeloproliferative neoplasms (MPN). The reagents can be used with peripheral whole blood (collected in K2EDTA, Acid Citrate Dextrose (ACD) or Heparin), bone marrow (collected in K2EDTA, ACD or Heparin) and lymph node specimens. Interpretation of the results should be confirmed by a pathologist or equivalent professional in conjunction with other clinical and laboratory findings.
These reagents provide multiparameter, qualitative results for the surface antigens listed below:
- ClearLLab 10C B Cell Tube: Kappa, Lambda, CD10, CD5, CD200, CD34, CD38, CD20, ● CD19. CD45
- . ClearLLab 10C T Cell Tube: TCRyS, CD4, CD2, CD56, CD5, CD34, CD3, CD8, CD7, CD45
- ClearLLab 10C M1 Cell Tube: CD16, CD7, CD10, CD13, CD64, CD34, CD14, HLA-● DR, CD11b, CD45
- ClearLLab 10C M2 Cell Tube: CD15, CD123, CD117, CD13, CD33, CD34, CD38, HLA-DR, CD19, CD45
Navios Flow Cytometer
The Navios Flow Cytometer is intended for use as an in vitro diagnostic device for immunophenotyping using up to ten fluorescent detection channels using three lasers (488 mm. 638 nm, and 405 nm) and two light scatter detection channels. It is intended for use with in vitro diagnostic (IVD) assays and software that are indicated for use with the instrument.
Navios EX Flow Cytometer
The Navios EX Flow Cytometer is intended for use as an in vitro diagnostic device for immunophenotyping using up to ten fluorescent detection channels using three lasers (488 mm, 638 nm, and 405 nm) and two light scatter detection channels. It is intended for use with in vitro diagnostic (IVD) assays and software that are indicated for use with the instrument.
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Technological Characteristics Comparisons to Predicate
| Table 1: Similarities of Features/Characteristics between the Predicate and Subject Device | |
|---|---|
| -- | -------------------------------------------------------------------------------------------- |
| Characteristic | New ClearLLab 10C Reagent System
Subject Device | Predicate ClearLLab Reagents (5-color)
(De Novo DEN160047) | | | | | | | |
|-----------------------------------------|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|----------|----------|-------------------------------------------------------------------------------------------|----------|----------|----------|---------|
| FDA product code | PWD
(based on De Novo submission DEN160047) | PWD | | | | | | | |
| Intended Use | In vitro diagnostic device for immunophenotyping | In vitro diagnostic device for immunophenotyping | | | | | | | |
| Indications for Use | SAME (with the exception of cytometer and clarifying
language)
Intended for in vitro diagnostic use as a panel for qualitative
identification of cell populations by multiparameter
immunophenotyping on the Navios and Navios EX flow
cytometers. These reagents are used as an aid in the
differential diagnosis of hematologically abnormal patients
having the following hematopoietic neoplasms: chronic
leukemia, acute leukemia, non-Hodgkin lymphoma,
myeloma, myelodysplastic syndrome (MDS), and/or
myeloproliferative neoplasms (MPN). The reagents can be
used with peripheral whole blood (collected in K2EDTA,
ACD or Heparin), bone marrow (collected in K2EDTA, ACD
or Heparin) and lymph node specimens for
immunophenotyping. Interpretation of the results should be
confirmed by a pathologist or equivalent in conjunction with
other clinical and laboratory findings. | Intended for in vitro diagnostic use as a panel for qualitative
identification of cell populations by immunophenotyping on an
FC 500 flow cytometer. These reagents are used as an aid in
the differential diagnosis of hematologically abnormal patients
having the following hematopoietic neoplasms: chronic
leukemia, acute leukemia, non-Hodgkin lymphoma, myeloma,
myelodysplastic syndrome (MDS), and/or myeloproliferative
neoplasms (MPN). The reagents can be used with peripheral
whole blood (collected in K2EDTA, ACD or Heparin), bone
marrow (collected in K2EDTA, ACD or Heparin) and lymph
node specimens for immunophenotyping. The results should
be interpreted by a pathologist or equivalent in conjunction
with other clinical and laboratory findings. | | | | | | | |
| Reagent Panels | BOLDED MARKERS ARE THE SAME | | | | | | | | |
| | B panel | T panel | M1 panel | M2 panel | B1 panel | B2 panel | T1 panel | T2 panel | M panel |
| | KAPPA | TCRγδ | CD16 | CD15 | CD2 | CD8 | KAPPA | CD20 | CD7 |
| | LAMBDA | CD4 | CD7 | CD123 | CD56 | CD4 | LAMBDA | CD10 | CD13 |
| | CD10 | CD2 | CD10 | CD117 | CD7 | | CD19 | CD19 | CD34 |
| Characteristic | New ClearLLab 10C Reagent System
Subject Device | | | | Predicate ClearLLab Reagents (5-color)
(De Novo DEN160047) | | | | |
| | CD5 | CD56 | CD13 | CD13 | CD5 | CD3 | CD5 | CD38 | CD33 |
| | CD200 | CD5 | CD64 | CD33 | CD45 | CD45 | CD45 | CD45 | CD4 |
| | CD34 | CD34 | CD34 | CD34 | | | | | |
| | CD38 | CD7 | CD14 | CD38 | | | | | |
| | CD20 | CD8 | HLA-DR | HLA-DR | | | | | |
| | CD19 | CD3 | CD11b | CD19 | | | | | |
| | CD45 | CD45 | CD45 | CD45 | | | | | |
| Reagent Form | Dry unitized form (one test / panel) | | | | Liquid form | | | | |
| Storage Conditions | 18-30°C | | | | 2-8°C | | | | |
| Set-up Reagents
Standardization | SIMILAR
Flow-Set Pro Fluorospheres:
Same function, but expanded to allow use on all 10 channels
of the Navios and Navios EX | | | | Flow-Set Pro Fluorospheres | | | | |
| Optical alignment and
fluidics | SIMILAR
Flow-Check Pro Fluorospheres:
Same function, but expanded to allow use on all 10 channels
of the Navios and Navios EX | | | | Flow-Check Pro Fluorospheres | | | | |
| Lyse and Fixation | SIMILAR, EXISTING
IOTest 3 Fixative Solution
IOTest 3 Lysing Solution | | | | IOTest 3 Fixative Solution
VersaLyse Lysing Solution | | | | |
| Sample Preparation | SIMILAR
Wash and prepare samples manually | | | | Wash and prepare samples manually | | | | |
| Reagents for Color | NEW | | | | | | | | |
| Compensation
ClearLLab Compensation | ClearLLab Compensation Kit with ClearLLab Compensation | | | | | | | | |
| Kit and ClearLLab
Compensation Beads | Beads: the Compensation Kit includes dry reagents used to
set color compensation settings. The kit contains 10 tubes of
a single color reagent per use, each containing a single
antibody conjugated to a specific fluorochrome. The
Compensation Beads are positive and negative microspheres | | | | CD45-FITC, CD45-PE and CD45-ECD from existing
QuickComp 4 plus CD45-PC5.5 and CD45-PC7 | | | | |
10
11
| Characteristic | New ClearLLab 10C Reagent System
Subject Device | Predicate ClearLLab Reagents (5-color)
(De Novo DEN160047) |
|----------------|-----------------------------------------------------------------------------------|---------------------------------------------------------------|
| | that can be used to set compensation in conjunction with the
Compensation Kit. | |
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| Table 2: Similarities and differences between Navios and its predicate |
|---|
| Attribute | Navios Flow Cytometer
K130373 | Subject Navios Flow Cytometer |
|-----------------------------------------------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| FDA product code | OYE | OYE |
| Indications for Use | The Navios Flow Cytometer is intended for use as an in vitro
diagnostic device for immunophenotyping. It can be used in
conjunction with the following monoclonal antibody reagents
and software package:
CYTO-STAT tetraCHROME CD45-FITC/CD4-
RD1/CD8-ECD/CD3-PC5 and CYTO-STATE
tetraCHROME CD45-FITC/CD56-RD1/CD19-
ECD/CD3-PCD5 monoclonal antibody reagents. These
reagents provide identification and enumeration of
CD3+CD4+, CD3+CD8+, CD3+, CD19+ and CD3-
CD56+ lymphocyte percentages and absolute counts in
peripheral whole blood. Absolute counts may be
determined by the Navios flow cytometer using Flow-
Count Fluorospheres (single platform technology
method) or separate hematology results (dual platform
method). These reagents are indicated for use in the
immunologic assessment of patients having or
suspected of having immune deficiency. Navios tetra Software for automated analysis and
results with CYTO-STAT tetraCHROME CD45-
FITC/CD4-RD1/CD8-ECD/CD3-PC5 and CYTO-
STAT tetraCHROME CD45-FITC/CD56-RD1/CD19-
ECD/CD3-PC5 monoclonal antibody reagents. Navios Software may be installed on an independent computer
workstation for off-line analysis of listmode files generated by
the Navios Flow Cytometer with the monoclonal antibody
reagents and software package listed above. The off-line analysis
must be performed in accordance with the product labeling. | The Navios Flow Cytometer is intended for use as an in vitro
diagnostic device for immunophenotyping using up to ten
fluorescent detection channels using three lasers (488 nm, 638
nm and 405 nm) and two light scatter detection channels. It is
intended for use with in vitro diagnostic (IVD) assays and
software that are indicated for use with the instrument. |
| Safety Features | Interlocks and mitigation of hazards via software and hardware
controls | Same |
| Attribute | Navios Flow Cytometer
K130373 | Subject Navios Flow Cytometer |
| Pre-Analytic Features | | |
| System Configuration | Bench top Printer PC based workstation running Microsoft Windows Vista or WIN7 application specific software | Same (the 10C application is for WIN7 only) |
| Sample Preparation with Monoclonal Antibodies | Off-board sample preparation following instructions provided with cleared antibody reagent | Same |
| Sample Presentation | Prepared sample added to a daughter tube | Same |
| Sample Aspiration Probe | Fixed height | Same |
| Resuspension of prepared sample prior to introduction to system | Prepared sample is vortex mixed | Same |
| Sample Introduction | Tube sampler Automated presentation with Multi-tube Carousel Loader (MCL) from 32 test tube capacity carousel Manual presentation into a tube location on a MCL via tube access door | Same |
| Aspiration Pathway | Same aspiration pathway used for automated and manual presentation | Same |
| Sample Identification | Bar-code reading of carousel position and labeled sample tube. User may also identify samples based on carousel location with a worklist. | Same |
| Analytical Features | | |
| Lasers / Driver Boards | Blue (488 nm), 22mW
Red (638 nm), 25mW
Violet (405 nm), 40mW | Same |
| Attribute | Navios Flow Cytometer
K130373 | Subject Navios Flow Cytometer |
| Maximum Parameter
Detectors | Twelve (FS, SS, FL1 – FL10) | Same |
| Electronics | 40 MHz sampling
Digital integrator circuitry w/ early stage ADC | Same |
| Photomultiplier Tubes
(PMTs) / Colors | Standard 5 PMTs (FL1 – FL5) off of 488 nm laser (blue) | Same; 10C application will require expansion to all 10 PMTs:
Standard 3 PMTs (FL6 – FL8) off of 638 nm laser (red)
Standard 2 PMTs (FL9 – FL10) off of 405 nm laser (violet) |
| Color Separation | Collimated beam is separated into desired components with
dichroic filters. | Same |
| On-board acquisition
software | System Software available | Same |
| Post-Analytical Features | | |
| Data Reporting | FlowPAGE, Panel Report, Plots and Statistics printouts | Same |
| Cleaning Cycle
Between Samples | Executed with IsoFlow Sheath Fluid ensuring carryover
specification is met | Same |
| Quality Control
Techniques | • Daily Instrument Checks
• Supplied Controls for ClearLLab 10C application
• Inter-laboratory Quality Assurance Program (IQAP) | Same |
| Cleanse Cycle | Cleaning cycle performed with FlowClean cleaning reagent as
part of the daily shutdown process, before and after running
samples with vital dyes that stain the tubing, and as part of
troubleshooting. | Same |
| Compensation and Sample Preparation Reagents | | |
| Reagents used for
compensation and
sample preparation | QuickComp 4 | ClearLLab Compensation Kit and Compensation Beads with the
new ClearLLab 10C application. |
| Controls and Calibrators | | |
| Assay Controls and
Calibrators | Flow-Check Pro Fluorospheres
Flow-Set Pro Fluorospheres | Same
Same function, but expanded to allow use on all 10 channels |
| Process Controls | Immuno-Trol and Immuno-Trol Low | ClearLLab Control Cells (Normal and Abnormal) with the
ClearLLab 10C application. |
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Table 3: Similarities and differences between Navios EX and its predicate
| Attribute | Navios EX Flow Cytometer
K162897 | Subject Navios EX Flow Cytometer |
|--------------------------------------------------------------------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Product Code | OYE | OYE |
| Indications for Use | The Navios EX Flow Cytometer is intended for use as an in vitro
diagnostic device for immunophenotyping using up to four
fluorescent detection channels using a blue (488 nm) laser and
two light scatter detection channels. It is intended for use with in
vitro diagnostic (IVD) assays and software that are indicated for
use with the instrument. | The Navios EX Flow Cytometer is intended for use as an in vitro
diagnostic device for immunophenotyping using up to ten
fluorescent detection channels using three lasers (488 nm, 638
nm and 405 nm) and two light scatter detection channels. It is
intended for use with in vitro diagnostic (IVD) assays and
software that are indicated for use with the instrument. |
| Safety Features | Interlocks and mitigation of hazards via software and hardware
controls | Same |
| Pre-Analytic Features | | |
| System Configuration | Bench top Printer PC based workstation running Microsoft WIN7 application specific software | Same |
| Sample Preparation
with Monoclonal
Antibodies | Off-board sample preparation following instructions provided
with cleared antibody reagent | Same |
| Sample Presentation | Prepared sample added to a daughter tube | Same |
| Sample Aspiration
Probe | Fixed height | Same |
| Resuspension of
prepared sample prior
to introduction to
system | Prepared sample is vortex mixed | Same |
| Sample Introduction | Tube sampler Automated presentation with Multi-tube Carousel Loader (MCL) from 32 test tube capacity carousel Manual presentation into a tube location on a MCL via tube access door | Same |
| Aspiration Pathway | Same aspiration pathway used for automated and manual presentation | Same |
| Attribute | Navios EX Flow Cytometer
K162897 | Subject Navios EX Flow Cytometer |
| Sample Identification | Bar-code reading of carousel position and labeled sample tube.
User may also identify samples based on carousel location with a worklist. | Same |
| Analytical Features | | |
| Lasers / Driver Boards | Blue (488 nm), 55mW
Red (638 nm), 50 mW
Violet (405 nm), 80 mW | Same |
| Maximum Parameter Detectors | Twelve (FS, SS, FL1 – FL10) | Same |
| Electronics | 40 MHz sampling
Digital integrator circuitry w/ early stage ADC | Same |
| Photomultiplier Tubes
(PMTs) / Colors | Standard 5 PMTs (FL1 – FL5) off of 488 nm laser (blue) | Same; 10C application will require expansion to all 10 PMTs:
Standard 3 PMTs (FL6 – FL8) off of 638 nm laser (red)
Standard 2 PMTs (FL9 – FL10) off of 405 nm laser (violet) |
| Color Separation | Collimated beam is separated into desired components with dichroic filters. | Same |
| On-board acquisition software | System Software available | Same |
| Post-Analytical Features | | |
| Data Reporting | FlowPAGE, Panel Report, Plots and Statistics printouts | Same |
| Cleaning Cycle
Between Samples | Executed with IsoFlow Sheath Fluid ensuring carryover specification is met | Same |
| Quality Control
Techniques | • Daily Instrument Checks
• Supplied Controls for ClearLLab 10C application
• Inter-laboratory Quality Assurance Program (IQAP) | Same |
| Cleanse Cycle | Cleaning cycle performed with FlowClean cleaning reagent as part of the daily shutdown process, before and after running samples with vital dyes that stain the tubing, and as part of troubleshooting. | Same |
| Compensation and Sample Preparation Reagents | | |
| Attribute | Navios EX Flow Cytometer
K162897 | Subject Navios EX Flow Cytometer |
| Reagents used for
compensation and
sample preparation | QuickComp 4 | ClearLLab Compensation Kit and Compensation Beads with the
new ClearLLab 10C application. |
| Controls and Calibrators | | |
| Assay Controls and
Calibrators | Flow-Check Pro Fluorospheres
Flow-Set Pro Fluorospheres | Same
Same function, but expanded to allow use on all 10 channels |
| Process Controls | Immuno-Trol and Immuno-Trol Low | ClearLLab Control Cells (Normal and Abnormal) with the
ClearLLab 10C application. |
16
17
18
| Study | Testing Approach | FDA Guidance Documents | Standards/ References | Testing Results |
|---|---|---|---|---|
| Laser Performance | ||||
| Characteristics | Verify stability of the laser | |||
| performance of the Navios | ||||
| and Navios EX flow | ||||
| cytometer over time. | None | None | Analysis of the data collected demonstrates | |
| that the Navios and Navios EX laser | ||||
| performance is stable over time. | ||||
| Instrument Carryover | To verify carryover using | |||
| Flow-Check Pro | ||||
| fluorospheres meets | ||||
| performance specifications. | Special Controls Guidance | |||
| Document: Premarket | ||||
| Notifications for Automated | ||||
| Differential Cell Counters | ||||
| for Immature or Abnormal | ||||
| Blood Cells - Carryover | ||||
| (Section 12) | CLSI H26-A2; FDA Standards | |||
| Recognition #7-210 | Analysis of the data collected demonstrates | |||
| that the Navios and Navios EX meet the | ||||
| carryover performance requirements. | ||||
| Instrument Linearity | Verify fluorescence detection | |||
| is linear using standard | ||||
| Navios and Navios EX | ||||
| settings. | None | None | Linearity of fluorescence measurements was | |
| demonstrated. | ||||
| Navios vs. Navios EX | ||||
| Percent Cell Recovery | ||||
| Equivalence Study | Demonstrate the equivalent | |||
| performance in % cell | ||||
| recovery between Navios and | ||||
| Navios EX flow cytometers | ||||
| when running ClearLLab 10C | ||||
| application. | Special Controls Guidance | |||
| Document: Premarket | ||||
| Notifications for Automated | ||||
| Differential Cell Counters | ||||
| for Immature or Abnormal | ||||
| Blood Cells - Accuracy | ||||
| (Section 8) | CLSI EP09-A3, Method | |||
| Comparison and Bias Estimation | ||||
| Using Patient Samples; Approved | ||||
| Guideline | Analysis of the data collected demonstrates | |||
| that the Navios and Navios EX Flow | ||||
| Cytometry Systems are equivalence when | ||||
| running the ClearLLab 10C application. | ||||
| Study | Objective | FDA Guidance Documents | Standards/ References | Testing Results |
| Characterization | Demonstrate antibody | |||
| specificity including | ||||
| Fluorescence Minus One | None | None | Analysis of the data collected demonstrates | |
| that specific antibody clones and polyclonal | ||||
| antibody reagents are identified for ClearLLab | ||||
| 10C reagent panel markers. | ||||
| Characterization | Titrate for optimal reagent | |||
| dosage | None | None | Analysis of the data collected demonstrates | |
| that antibody conjugates dosing values are | ||||
| determined for was defined for each antibody | ||||
| of ClearLLab 10C reagents. | ||||
| Characterization | Assess of Non-Specific | |||
| Binding | None | None | Analysis of the data collected demonstrates | |
| solutions implemented to reduce and/or obtain | ||||
| acceptable level of non-specific binding. | ||||
| Lot-to-Lot Reproducibility | Demonstrate variability of | |||
| multiple lots of material. | None | CLSI EP5-A3, Evaluation of | ||
| Precision Performance of | ||||
| Quantitative Measurement | ||||
| Methods: Approved Guideline - | ||||
| Third Edition. FDA Standards | ||||
| Recognition #7-251 | Analysis of the data collected demonstrates | |||
| that the ClearLLab 10C panels have | ||||
| acceptable lot variability performance. | ||||
| Stability | Demonstrate reagent stability. | None | CLSI EP25-A - Evaluation of | |
| Stability of In Vitro Diagnostic | ||||
| Reagents. Approved Guideline | Analysis of the data collected demonstrates | |||
| that the ClearLLab 10C panels met | ||||
| performance requirements in support of the | ||||
| product's stability claims. | ||||
| Carryover - Specimen and | ||||
| Reagent | To verify carryover of | |||
| specimen and reagents on the | ||||
| Navios and Navios EX meets | ||||
| performance specifications. | Special Controls Guidance | |||
| Document: Premarket | ||||
| Notifications for | ||||
| Automated Differential | ||||
| Cell Counters for Immature | ||||
| or Abnormal Blood Cells - | ||||
| Carryover (Section 12) | Validation, Verification, and | |||
| Quality Assurance of Automated | ||||
| Hematology Analyzers, Approved | ||||
| Standard - 2nd Edition; June 2010; | ||||
| CLSI H26-A2; FDA Standards | ||||
| Recognition #7-210 | Analysis of the data collected demonstrates | |||
| that the Navios and Navios EX meets | ||||
| carryover performance requirements. | ||||
| Bulk vs. Single Wash | Demonstrate equivalency of | |||
| sample preparation methods. | None | CLSI EP09-A3, Measurement | ||
| Procedure Comparison and Bias | Equivalency of single tube wash and bulk | |||
| wash methodology was demonstrated. | ||||
| Study | Objective | FDA Guidance Documents | Standards/ References | Testing Results |
| Detection Capability | To verify that the ClearLLab | |||
| 10C panels with the Navios or | ||||
| Navios EX meet the | ||||
| performance requirements for | ||||
| the ability to differentiate | ||||
| between abnormal and normal | ||||
| populations. | None | Estimation Using Patient Samples; | ||
| Approved Guideline |
Wood B et al. Validation of Cell-
Based Fluorescence Assays:
Practice Guidelines from the ICSH
and ICCS - Part V - Assay
performance Criteria. Cytometry
Part B (Clinical Cytometry), pp.
315-323 | Analysis of the data collected demonstrates
that the ClearLLab 10C panels with the
Navios or Navios EX meet the performance
requirements for Detection Capability. |
| Specimen Age and
Prepared Sample Stability
(Whole Blood and Bone
Marrow) | Verify whole blood and bone
marrow specimen and
prepared sample stability
claims. | None | None | Analysis of the data collected demonstrates
that the ClearLLab 10C panels meet the
requirements for specimen and prepared
sample stability (Whole Blood and Bone
Marrow). |
| Specimen Age and
Prepared Sample Stability
(Lymph Node) | Verify lymph node samples
prepared sample stability
claim. | None | None | Analysis of the data collected demonstrates
that the ClearLLab 10C panels meet the
requirements for prepared sample stability
(Lymph Node). |
| Anticoagulant Equivalency
– Whole Blood | Demonstrate equivalent
performance of whole blood
specimens collected in several
different anticoagulants
(K2EDTA, Heparin and ACD)
on the Navios system using
ClearLLab 10C panels. | None | CLSI EP09-A3, Measurement
Procedure Comparison and Bias
Estimation Using Patient Samples;
Approved Guideline--Third Edition | Performance of ClearLLab 10C panels with
whole blood specimens collected in K2EDTA,
Heparin and ACD anticoagulants was
demonstrated to be equivalent. |
| Anticoagulant Method
Comparison - 10C to 5C | Demonstrate equivalency of
anticoagulants used with bone
marrow and whole blood
specimens with the ClearLLab
10C panels in reference to the
ClearLLab 5 color reagents. | Special Controls Guidance
Document: Premarket
Notifications for
Automated Differential
Cell Counters for Immature
or Abnormal Blood Cells -
Accuracy (Section 8) | User Protocol for Evaluation of
Qualitative Test Performance:
Approved Guideline – Second
Edition; CLSI EP12-A2; FDA
Standards Recognition #7-152 | For all conditions evaluated, the data collected
demonstrates that the various anticoagulants
are equivalent. |
| Study | Objective | FDA Guidance Documents | Standards/ References | Testing Results |
| Precision - Control
Material | Demonstrate system
imprecision using control
material as a surrogate for a
stabilized sample | Special Controls Guidance
Document: Premarket
Notifications for
Automated Differential
Cell Counters for Immature
or Abnormal Blood Cells -
Precision (Section 9) | CLSI EP5-A3, Evaluation of
Precision of Quantitative
Measurement Procedures;
Approved Guideline - Third
Edition. FDA Standards
Recognition #7-251 | Analysis of the data collected demonstrates
that the ClearLLab 10C panels meet
performance requirements for repeatability
and reproducibility. |
| Precision - Multi-Site with
Clinical Specimens | Demonstrate assay
repeatability and
reproducibility using both
normal and clinical
specimens. | Special Controls Guidance
Document: Premarket
Notifications for
Automated Differential
Cell Counters for Immature
or Abnormal Blood Cells -
Precision (Section 9) | CLSI EP5-A3. Evaluation of
Precision of Quantitative
Measurement Procedures;
Approved Guideline - Third
Edition. FDA Standards
Recognition #7-251
User Protocol for Evaluation of
Qualitative Test Performance;
Approved Guideline - Second
Edition; CLSI EP12-A2; FDA
Standards Recognition #7-152 | Analysis of the data collected demonstrates
that the ClearLLab 10C panels meet
performance requirements for repeatability
and reproducibility. |
| Precision - Operator and
Instrument Variability | Demonstrate system
imprecision performance of
the ClearLLab 10C panels
using the same specimen
prepared by three (3)
operators, twice a day, on two
(2) Navios EX flow
cytometers. | Special Controls Guidance
Document: Premarket
Notifications for
Automated Differential
Cell Counters for Immature
or Abnormal Blood Cells -
Precision (Section 9) | CLSI EP5-A3, Evaluation of
Precision of Quantitative
Measurement Procedures:
Approved Guideline - Third
Edition. FDA Standards
Recognition #7-251
User Protocol for Evaluation of
Qualitative Test Performance:
Approved Guideline - Second
Edition; CLSI EP12-A2; FDA
Standards Recognition #7-152 | The ClearLLab 10C panels when run on each
specimen type by different operators on
different Navios EX flow cytometers
demonstrated acceptable precision
performance and met acceptance criteria. |
| Clinical Accuracy | Evaluate the clinical accuracy
of the ClearLLab 10C Panels
in identifying an abnormal or
normal phenotype vs. the | None | CLSI H43-A2: Clinical Flow
Cytometric Analysis of Neoplastic
Hematolymphoid Cells - Second | Analysis of the data collected demonstrates
that the ClearLLab 10C panels are able |
| Study | Objective | FDA Guidance Documents | Standards/ References | Testing Results |
| | site's clinical diagnosis of
malignant or non-malignant
outcome from the current
standard of care | | Edition; FDA Standards
Recognition #7-150
User Protocol for Evaluation of
Qualitative Test Performance;
Approved Guideline – Second
Edition; CLSI EP12-A2; FDA
Standards Recognition #7-152
CLSI EP24-A2: Assessment of the
Diagnostic Accuracy of Laboratory
Tets Using Receiver Operating
Characteristic Curves; Approved
Guideline – Second Edition; FDA
Standards Recognition #7-234 | identify the abnormal population when
compared to clinical outcome. |
| Study | Objective | FDA Guidance Documents | Standards/ References | Testing Results |
| IOTest 3 Fixative and
IOTest 3 Lysing Solution -
Lot-to-Lot Reproducibility | Demonstrate variability of
multiple lots of material. | None | CLSI EP5-A3, Evaluation of
Precision of Quantitative
Measurement Procedures; Approved
Guideline - Third Edition. FDA
Standards Recognition #7-251 | Analysis of the data collected demonstrates
that the IOTest 3 Fixative and Lysing
Solutions have acceptable lot variability
performance. |
| Flow-Set Pro Lot-to-Lot
Variability | Demonstrate variability of
multiple lots of material. | None | CLSI EP5-A3, Evaluation of
Precision of Quantitative
Measurement Procedures: Approved
Guideline - Third Edition. FDA
Standards Recognition #7-251 | Analysis of the data collected demonstrates
that the Flow-Set Pro have acceptable lot
variability performance. |
| Flow-Check Pro Lot-to-Lot
Variability | Demonstrate variability of
multiple lots of material. | None | CLSI EP5-A3, Evaluation of
Precision of Quantitative
Measurement Procedures; Approved
Guideline - Third Edition. FDA
Standards Recognition #7-251 | Analysis of the data collected demonstrates
that the Flow-Check Pro have acceptable lot
variability performance. |
| ClearLLab Compensation
Kit with ClearLLab
Compensation Beads
Reagent Stability | Demonstrate reagent
stability. | None | None | Analysis of the data collected demonstrates
that the Compensation Kit and Compensation
Beads meet performance requirements in
support of the products' stability claims. |
| IOTest 3 Lysing Solution
and Fixative Reagent
Stability | Demonstrate reagent
stability. | None | None | Analysis of the data collected demonstrates
that the IOTest 3 Fixative Solution and
Lysing Solutions meet performance
requirements in support of the product's
stability claims. |
| Flow-Set Pro Fluorospheres
Reagent Stability | Demonstrate reagent
stability. | None | CLSI EP25-A - Evaluation of
Stability of In Vitro Diagnostic
Reagents. Approved Guideline:
FDA Standards Recognition #7-235 | Analysis of the data collected demonstrates
that the Flow-Set Pro Fluorospheres meet
performance requirements in support of the
product's stability claims. |
| Flow-Check Pro
Fluorospheres Reagent
Stability | Demonstrate reagent
stability. | None | CLSI EP25-A – Evaluation of
Stability of In Vitro Diagnostic
Reagents. Approved Guideline:
FDA Standards Recognition #7-235 | Analysis of the data collected demonstrates
that the Flow-Check Pro Fluorospheres meet
performance requirements in support of the
product's stability claims. |
| Flow-Set Pro Analyte
Value Assignment | Define Flow-Set Pro Target
ranges for use with the
ClearLLab 10C panels and
define a process for ranges
transfer from one lot of Flow-
Set Pro Fluorospheres. | None | None | Analysis of the data collected demonstrates
that appropriate Flow-Set Pro target ranges
are defined for use with the ClearLLab 10C
panels and that a process for ranges transfer
from one lot of Flow-Set Pro Fluorospheres
to another one is in place. |
Summary of Instrument Characterization and Analytical Performance Testing
19
Summary of ClearLLab 10C Reagents (T, B, M1, M2) Performance Testing:
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21
22
23
Summary of Accessory Reagents Performance Testing:
24
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Substantial Equivalence Conclusion to Demonstrate Safety, Effectiveness & Equivalent Performance to Predicate:
The ClearLLab 10C Reagents, that are the subject of this submission, in concert with the conclusions drawn from the performance testing discussed above demonstrate that when compared to the predicate device is as safe, as effective, and meets the performance acceptance criteria.
In summary, the ClearLLab 10C Reagents as described in this submission is substantially equivalent in terms of safety and effectiveness to its predicate devices.
- . The ClearLLab 10C Reagents are substantially equivalent to the ClearLLab Reagents (5C).
This summary of safety and effectiveness is being submitted in accordance with the requirements of the Safe Medical Device Act of 1990 and the implementing regulation 21 CFR 807.92.