(90 days)
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
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.
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.
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.
The provided text describes the ClearLLab 10C Panels and associated Navios and Navios EX Flow Cytometers. Here's a breakdown of the acceptance criteria and study information:
1. Table of Acceptance Criteria and Reported Device Performance
The document does not explicitly present a single table delineating acceptance criteria and reported device performance for each metric. Instead, it lists various studies performed, their objectives, and their results, which implicitly demonstrate an acceptance of performance. The "Testing Results" column in the tables effectively serves as the "Reported Device Performance," and the objective of each study implies the acceptance criteria (i.e., demonstrating stability, linearity, equivalency, specificity, etc.).
Below is a summary derived from the "Testing Results" section (pages 18-19):
ClearLLab 10C Panels, Navios and Navios EX Flow Cytometers Acceptance Criteria and Performance Summary
| Study Name | Objective (Implied Acceptance Criteria) | Reported Device Performance |
|---|---|---|
| Laser Performance Characteristics | Verify stability of the laser performance of the Navios and Navios EX flow cytometer over time. | Navios and Navios EX laser performance is stable over time. |
| Instrument Carryover | Verify carryover using Flow-Check Pro fluorospheres meets performance specifications. | Navios and Navios EX meet the carryover performance requirements. |
| Instrument Linearity | Verify fluorescence detection is linear using standard Navios and Navios EX settings. | 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. | Navios and Navios EX Flow Cytometry Systems are equivalent when running the ClearLLab 10C application. |
| Antibody Specificity Characterization | Demonstrate antibody specificity including Fluorescence Minus One. | Specific antibody clones and polyclonal antibody reagents are identified for ClearLLab 10C reagent panel markers. |
| Reagent Dosing Characterization | Titrate for optimal reagent dosage. | Antibody conjugate dosing values were defined for each antibody of ClearLLab 10C reagents. |
| Non-Specific Binding Characterization | Assess of Non-Specific Binding. | Solutions implemented to reduce and/or obtain acceptable level of non-specific binding. |
| Lot-to-Lot Reproducibility (ClearLLab 10C panels) | Demonstrate variability of multiple lots of material. | The ClearLLab 10C panels have acceptable lot variability performance. |
| Stability (ClearLLab 10C panels) | Demonstrate reagent stability. | The ClearLLab 10C panels met performance requirements in support of the product's stability claims. |
| Carryover - Specimen and Reagent | Verify carryover of specimen and reagents on the Navios and Navios EX meets performance specifications. | The Navios and Navios EX meet carryover performance requirements. |
| Bulk vs. Single Wash | Demonstrate equivalency of sample preparation methods. | Equivalency of single tube wash and bulk wash methodology was demonstrated. |
| Detection Capability | 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. | 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. | 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. | 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. | 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. | For all conditions evaluated, the data collected demonstrates that the various anticoagulants are equivalent. |
| Precision - Control Material | Demonstrate system imprecision using control material as a surrogate for a stabilized sample. | 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. | 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. | 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 site's clinical diagnosis of malignant or non-malignant outcome from the current standard of care. | The ClearLLab 10C panels are able to identify the abnormal population when compared to clinical outcome. |
| IOTest 3 Fixative and IOTest 3 Lysing Solution - Lot-to-Lot Reproducibility | Demonstrate variability of multiple lots of material. | 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. | The Flow-Set Pro have acceptable lot variability performance. |
| Flow-Check Pro Lot-to-Lot Variability | Demonstrate variability of multiple lots of material. | The Flow-Check Pro have acceptable lot variability performance. |
| ClearLLab Compensation Kit with ClearLLab Compensation Beads Reagent Stability | Demonstrate reagent stability. | 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. | 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. | 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. | 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. | 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. |
2. Sample Size Used for the Test Set and Data Provenance
- Sample Size for Test Set: The document does not specify a distinct "test set" sample size for all studies. However, for the "Precision - Multi-Site with Clinical Specimens" and "Precision - Operator and Instrument Variability" studies, typical clinical specimens (both normal and abnormal) were used. The specific number of specimens for each study is not explicitly stated in the provided text.
- Data Provenance: The document does not explicitly state the country of origin. The "Clinical Accuracy" study mentions "the site's clinical diagnosis," indicating that the data likely came from clinical sites where the study was conducted. The studies appear to be prospective in nature, as they involve actively verifying performance, stability, and equivalency.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
- For the "Clinical Accuracy" study, the comparison was made against "the site's clinical diagnosis of malignant or non-malignant outcome from the current standard of care." The interpretation of results for the device itself is stated to "be confirmed by a pathologist or equivalent professional in conjunction with other clinical and laboratory findings" (page 2). This indicates that pathologists or equivalent professionals establish the ground truth for clinical cases. The number of such experts is not specified.
4. Adjudication Method for the Test Set
- The document implies that the ground truth for "Clinical Accuracy" is established by "the site's clinical diagnosis...from the current standard of care" and confirmed by a "pathologist or equivalent professional." However, it does not explicitly describe an adjudication method (such as 2+1, 3+1, or none) for resolving discrepancies among multiple expert opinions on a specific case.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
- The provided text does not describe a multi-reader, multi-case (MRMC) comparative effectiveness study involving human readers with and without AI assistance (which is not relevant for this device as it's a diagnostic reagent and flow cytometer system, not an AI interpretative software for human review).
6. Standalone Performance Study
- The studies described, particularly those evaluating laser performance, instrument linearity, carryover, and reagent characteristics, are inherently standalone (algorithm/system only) performance studies. The system is evaluated on its ability to accurately detect and characterize cell populations. The "Clinical Accuracy" study also assesses the device's ability to identify abnormal populations against clinical outcomes, which is a standalone evaluation of its diagnostic capability.
7. Type of Ground Truth Used
- For various analytical studies (e.g., linearity, carryover, precision), the ground truth is established by reference standards, control materials, and comparative methods (e.g., predicate devices).
- For the "Clinical Accuracy" study, the ground truth is based on clinical diagnosis of malignant or non-malignant outcome from the current standard of care, confirmed by pathologist or equivalent professional consensus in conjunction with other clinical and laboratory findings.
8. Sample Size for the Training Set
- The document does not explicitly mention a "training set" as the devices described are diagnostic reagents and flow cytometers, not AI models that require specific training data in the context of machine learning. The studies listed are for performance verification and validation.
9. How the Ground Truth for the Training Set Was Established
- As there is no explicit mention of a "training set" in the context of an AI/machine learning model, this information is not applicable and is not provided in the document.
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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
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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."
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| 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 | DateCleared | Classification | 21 CFR | ProductCode |
|---|---|---|---|---|---|
| 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.
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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 SystemSubject 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 clarifyinglanguage)Intended for in vitro diagnostic use as a panel for qualitativeidentification of cell populations by multiparameterimmunophenotyping on the Navios and Navios EX flowcytometers. These reagents are used as an aid in thedifferential diagnosis of hematologically abnormal patientshaving the following hematopoietic neoplasms: chronicleukemia, acute leukemia, non-Hodgkin lymphoma,myeloma, myelodysplastic syndrome (MDS), and/ormyeloproliferative neoplasms (MPN). The reagents can beused with peripheral whole blood (collected in K2EDTA,ACD or Heparin), bone marrow (collected in K2EDTA, ACDor Heparin) and lymph node specimens forimmunophenotyping. Interpretation of the results should beconfirmed by a pathologist or equivalent in conjunction withother clinical and laboratory findings. | Intended for in vitro diagnostic use as a panel for qualitativeidentification of cell populations by immunophenotyping on anFC 500 flow cytometer. These reagents are used as an aid inthe differential diagnosis of hematologically abnormal patientshaving the following hematopoietic neoplasms: chronicleukemia, acute leukemia, non-Hodgkin lymphoma, myeloma,myelodysplastic syndrome (MDS), and/or myeloproliferativeneoplasms (MPN). The reagents can be used with peripheralwhole blood (collected in K2EDTA, ACD or Heparin), bonemarrow (collected in K2EDTA, ACD or Heparin) and lymphnode specimens for immunophenotyping. The results shouldbe interpreted by a pathologist or equivalent in conjunctionwith 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 SystemSubject 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 ReagentsStandardization | SIMILARFlow-Set Pro Fluorospheres:Same function, but expanded to allow use on all 10 channelsof the Navios and Navios EX | Flow-Set Pro Fluorospheres | |||||||
| Optical alignment andfluidics | SIMILARFlow-Check Pro Fluorospheres:Same function, but expanded to allow use on all 10 channelsof the Navios and Navios EX | Flow-Check Pro Fluorospheres | |||||||
| Lyse and Fixation | SIMILAR, EXISTINGIOTest 3 Fixative SolutionIOTest 3 Lysing Solution | IOTest 3 Fixative SolutionVersaLyse Lysing Solution | |||||||
| Sample Preparation | SIMILARWash and prepare samples manually | Wash and prepare samples manually | |||||||
| Reagents for Color | NEW | ||||||||
| CompensationClearLLab Compensation | ClearLLab Compensation Kit with ClearLLab Compensation | ||||||||
| Kit and ClearLLabCompensation Beads | Beads: the Compensation Kit includes dry reagents used toset color compensation settings. The kit contains 10 tubes ofa single color reagent per use, each containing a singleantibody conjugated to a specific fluorochrome. TheCompensation Beads are positive and negative microspheres | CD45-FITC, CD45-PE and CD45-ECD from existingQuickComp 4 plus CD45-PC5.5 and CD45-PC7 |
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| Characteristic | New ClearLLab 10C Reagent SystemSubject Device | Predicate ClearLLab Reagents (5-color)(De Novo DEN160047) |
|---|---|---|
| that can be used to set compensation in conjunction with theCompensation Kit. |
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| Table 2: Similarities and differences between Navios and its predicate |
|---|
| Attribute | Navios Flow CytometerK130373 | Subject Navios Flow Cytometer |
|---|---|---|
| FDA product code | OYE | OYE |
| Indications for Use | The Navios Flow Cytometer is intended for use as an in vitrodiagnostic device for immunophenotyping. It can be used inconjunction with the following monoclonal antibody reagentsand software package:CYTO-STAT tetraCHROME CD45-FITC/CD4-RD1/CD8-ECD/CD3-PC5 and CYTO-STATEtetraCHROME CD45-FITC/CD56-RD1/CD19-ECD/CD3-PCD5 monoclonal antibody reagents. Thesereagents provide identification and enumeration ofCD3+CD4+, CD3+CD8+, CD3+, CD19+ and CD3-CD56+ lymphocyte percentages and absolute counts inperipheral whole blood. Absolute counts may bedetermined by the Navios flow cytometer using Flow-Count Fluorospheres (single platform technologymethod) or separate hematology results (dual platformmethod). These reagents are indicated for use in theimmunologic assessment of patients having orsuspected of having immune deficiency. Navios tetra Software for automated analysis andresults 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 computerworkstation for off-line analysis of listmode files generated bythe Navios Flow Cytometer with the monoclonal antibodyreagents and software package listed above. The off-line analysismust be performed in accordance with the product labeling. | The Navios Flow Cytometer is intended for use as an in vitrodiagnostic device for immunophenotyping using up to tenfluorescent detection channels using three lasers (488 nm, 638nm and 405 nm) and two light scatter detection channels. It isintended for use with in vitro diagnostic (IVD) assays andsoftware that are indicated for use with the instrument. |
| Safety Features | Interlocks and mitigation of hazards via software and hardwarecontrols | Same |
| Attribute | Navios Flow CytometerK130373 | 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), 22mWRed (638 nm), 25mWViolet (405 nm), 40mW | Same |
| Attribute | Navios Flow CytometerK130373 | Subject Navios Flow Cytometer |
| Maximum ParameterDetectors | Twelve (FS, SS, FL1 – FL10) | Same |
| Electronics | 40 MHz samplingDigital 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 withdichroic filters. | Same |
| On-board acquisitionsoftware | System Software available | Same |
| Post-Analytical Features | ||
| Data Reporting | FlowPAGE, Panel Report, Plots and Statistics printouts | Same |
| Cleaning CycleBetween Samples | Executed with IsoFlow Sheath Fluid ensuring carryoverspecification is met | Same |
| Quality ControlTechniques | • 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 aspart of the daily shutdown process, before and after runningsamples with vital dyes that stain the tubing, and as part oftroubleshooting. | Same |
| Compensation and Sample Preparation Reagents | ||
| Reagents used forcompensation andsample preparation | QuickComp 4 | ClearLLab Compensation Kit and Compensation Beads with thenew ClearLLab 10C application. |
| Controls and Calibrators | ||
| Assay Controls andCalibrators | Flow-Check Pro FluorospheresFlow-Set Pro Fluorospheres | SameSame 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 theClearLLab 10C application. |
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Table 3: Similarities and differences between Navios EX and its predicate
| Attribute | Navios EX Flow CytometerK162897 | Subject Navios EX Flow Cytometer |
|---|---|---|
| Product Code | OYE | OYE |
| Indications for Use | The Navios EX Flow Cytometer is intended for use as an in vitrodiagnostic device for immunophenotyping using up to fourfluorescent detection channels using a blue (488 nm) laser andtwo light scatter detection channels. It is intended for use with invitro diagnostic (IVD) assays and software that are indicated foruse with the instrument. | The Navios EX Flow Cytometer is intended for use as an in vitrodiagnostic device for immunophenotyping using up to tenfluorescent detection channels using three lasers (488 nm, 638nm and 405 nm) and two light scatter detection channels. It isintended for use with in vitro diagnostic (IVD) assays andsoftware that are indicated for use with the instrument. |
| Safety Features | Interlocks and mitigation of hazards via software and hardwarecontrols | Same |
| Pre-Analytic Features | ||
| System Configuration | Bench top Printer PC based workstation running Microsoft WIN7 application specific software | Same |
| Sample Preparationwith MonoclonalAntibodies | Off-board sample preparation following instructions providedwith cleared antibody reagent | Same |
| Sample Presentation | Prepared sample added to a daughter tube | Same |
| Sample AspirationProbe | Fixed height | Same |
| Resuspension ofprepared sample priorto introduction tosystem | 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 CytometerK162897 | 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), 55mWRed (638 nm), 50 mWViolet (405 nm), 80 mW | Same |
| Maximum Parameter Detectors | Twelve (FS, SS, FL1 – FL10) | Same |
| Electronics | 40 MHz samplingDigital 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 CycleBetween Samples | Executed with IsoFlow Sheath Fluid ensuring carryover specification is met | Same |
| Quality ControlTechniques | • 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 CytometerK162897 | Subject Navios EX Flow Cytometer |
| Reagents used forcompensation andsample preparation | QuickComp 4 | ClearLLab Compensation Kit and Compensation Beads with thenew ClearLLab 10C application. |
| Controls and Calibrators | ||
| Assay Controls andCalibrators | Flow-Check Pro FluorospheresFlow-Set Pro Fluorospheres | SameSame 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 theClearLLab 10C application. |
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| Study | Testing Approach | FDA Guidance Documents | Standards/ References | Testing Results |
|---|---|---|---|---|
| Laser PerformanceCharacteristics | Verify stability of the laserperformance of the Naviosand Navios EX flowcytometer over time. | None | None | Analysis of the data collected demonstratesthat the Navios and Navios EX laserperformance is stable over time. |
| Instrument Carryover | To verify carryover usingFlow-Check Profluorospheres meetsperformance specifications. | Special Controls GuidanceDocument: PremarketNotifications for AutomatedDifferential Cell Countersfor Immature or AbnormalBlood Cells - Carryover(Section 12) | CLSI H26-A2; FDA StandardsRecognition #7-210 | Analysis of the data collected demonstratesthat the Navios and Navios EX meet thecarryover performance requirements. |
| Instrument Linearity | Verify fluorescence detectionis linear using standardNavios and Navios EXsettings. | None | None | Linearity of fluorescence measurements wasdemonstrated. |
| Navios vs. Navios EXPercent Cell RecoveryEquivalence Study | Demonstrate the equivalentperformance in % cellrecovery between Navios andNavios EX flow cytometerswhen running ClearLLab 10Capplication. | Special Controls GuidanceDocument: PremarketNotifications for AutomatedDifferential Cell Countersfor Immature or AbnormalBlood Cells - Accuracy(Section 8) | CLSI EP09-A3, MethodComparison and Bias EstimationUsing Patient Samples; ApprovedGuideline | Analysis of the data collected demonstratesthat the Navios and Navios EX FlowCytometry Systems are equivalence whenrunning the ClearLLab 10C application. |
| Study | Objective | FDA Guidance Documents | Standards/ References | Testing Results |
| Characterization | Demonstrate antibodyspecificity includingFluorescence Minus One | None | None | Analysis of the data collected demonstratesthat specific antibody clones and polyclonalantibody reagents are identified for ClearLLab10C reagent panel markers. |
| Characterization | Titrate for optimal reagentdosage | None | None | Analysis of the data collected demonstratesthat antibody conjugates dosing values aredetermined for was defined for each antibodyof ClearLLab 10C reagents. |
| Characterization | Assess of Non-SpecificBinding | None | None | Analysis of the data collected demonstratessolutions implemented to reduce and/or obtainacceptable level of non-specific binding. |
| Lot-to-Lot Reproducibility | Demonstrate variability ofmultiple lots of material. | None | CLSI EP5-A3, Evaluation ofPrecision Performance ofQuantitative MeasurementMethods: Approved Guideline -Third Edition. FDA StandardsRecognition #7-251 | Analysis of the data collected demonstratesthat the ClearLLab 10C panels haveacceptable lot variability performance. |
| Stability | Demonstrate reagent stability. | None | CLSI EP25-A - Evaluation ofStability of In Vitro DiagnosticReagents. Approved Guideline | Analysis of the data collected demonstratesthat the ClearLLab 10C panels metperformance requirements in support of theproduct's stability claims. |
| Carryover - Specimen andReagent | To verify carryover ofspecimen and reagents on theNavios and Navios EX meetsperformance specifications. | Special Controls GuidanceDocument: PremarketNotifications forAutomated DifferentialCell Counters for Immatureor Abnormal Blood Cells -Carryover (Section 12) | Validation, Verification, andQuality Assurance of AutomatedHematology Analyzers, ApprovedStandard - 2nd Edition; June 2010;CLSI H26-A2; FDA StandardsRecognition #7-210 | Analysis of the data collected demonstratesthat the Navios and Navios EX meetscarryover performance requirements. |
| Bulk vs. Single Wash | Demonstrate equivalency ofsample preparation methods. | None | CLSI EP09-A3, MeasurementProcedure Comparison and Bias | Equivalency of single tube wash and bulkwash methodology was demonstrated. |
| Study | Objective | FDA Guidance Documents | Standards/ References | Testing Results |
| Detection Capability | To verify that the ClearLLab10C panels with the Navios orNavios EX meet theperformance requirements forthe ability to differentiatebetween abnormal and normalpopulations. | None | Estimation Using Patient Samples;Approved GuidelineWood B et al. Validation of Cell-Based Fluorescence Assays:Practice Guidelines from the ICSHand ICCS - Part V - Assayperformance Criteria. CytometryPart B (Clinical Cytometry), pp.315-323 | Analysis of the data collected demonstratesthat the ClearLLab 10C panels with theNavios or Navios EX meet the performancerequirements for Detection Capability. |
| Specimen Age andPrepared Sample Stability(Whole Blood and BoneMarrow) | Verify whole blood and bonemarrow specimen andprepared sample stabilityclaims. | None | None | Analysis of the data collected demonstratesthat the ClearLLab 10C panels meet therequirements for specimen and preparedsample stability (Whole Blood and BoneMarrow). |
| Specimen Age andPrepared Sample Stability(Lymph Node) | Verify lymph node samplesprepared sample stabilityclaim. | None | None | Analysis of the data collected demonstratesthat the ClearLLab 10C panels meet therequirements for prepared sample stability(Lymph Node). |
| Anticoagulant Equivalency– Whole Blood | Demonstrate equivalentperformance of whole bloodspecimens collected in severaldifferent anticoagulants(K2EDTA, Heparin and ACD)on the Navios system usingClearLLab 10C panels. | None | CLSI EP09-A3, MeasurementProcedure Comparison and BiasEstimation Using Patient Samples;Approved Guideline--Third Edition | Performance of ClearLLab 10C panels withwhole blood specimens collected in K2EDTA,Heparin and ACD anticoagulants wasdemonstrated to be equivalent. |
| Anticoagulant MethodComparison - 10C to 5C | Demonstrate equivalency ofanticoagulants used with bonemarrow and whole bloodspecimens with the ClearLLab10C panels in reference to theClearLLab 5 color reagents. | Special Controls GuidanceDocument: PremarketNotifications forAutomated DifferentialCell Counters for Immatureor Abnormal Blood Cells -Accuracy (Section 8) | User Protocol for Evaluation ofQualitative Test Performance:Approved Guideline – SecondEdition; CLSI EP12-A2; FDAStandards Recognition #7-152 | For all conditions evaluated, the data collecteddemonstrates that the various anticoagulantsare equivalent. |
| Study | Objective | FDA Guidance Documents | Standards/ References | Testing Results |
| Precision - ControlMaterial | Demonstrate systemimprecision using controlmaterial as a surrogate for astabilized sample | Special Controls GuidanceDocument: PremarketNotifications forAutomated DifferentialCell Counters for Immatureor Abnormal Blood Cells -Precision (Section 9) | CLSI EP5-A3, Evaluation ofPrecision of QuantitativeMeasurement Procedures;Approved Guideline - ThirdEdition. FDA StandardsRecognition #7-251 | Analysis of the data collected demonstratesthat the ClearLLab 10C panels meetperformance requirements for repeatabilityand reproducibility. |
| Precision - Multi-Site withClinical Specimens | Demonstrate assayrepeatability andreproducibility using bothnormal and clinicalspecimens. | Special Controls GuidanceDocument: PremarketNotifications forAutomated DifferentialCell Counters for Immatureor Abnormal Blood Cells -Precision (Section 9) | CLSI EP5-A3. Evaluation ofPrecision of QuantitativeMeasurement Procedures;Approved Guideline - ThirdEdition. FDA StandardsRecognition #7-251User Protocol for Evaluation ofQualitative Test Performance;Approved Guideline - SecondEdition; CLSI EP12-A2; FDAStandards Recognition #7-152 | Analysis of the data collected demonstratesthat the ClearLLab 10C panels meetperformance requirements for repeatabilityand reproducibility. |
| Precision - Operator andInstrument Variability | Demonstrate systemimprecision performance ofthe ClearLLab 10C panelsusing the same specimenprepared by three (3)operators, twice a day, on two(2) Navios EX flowcytometers. | Special Controls GuidanceDocument: PremarketNotifications forAutomated DifferentialCell Counters for Immatureor Abnormal Blood Cells -Precision (Section 9) | CLSI EP5-A3, Evaluation ofPrecision of QuantitativeMeasurement Procedures:Approved Guideline - ThirdEdition. FDA StandardsRecognition #7-251User Protocol for Evaluation ofQualitative Test Performance:Approved Guideline - SecondEdition; CLSI EP12-A2; FDAStandards Recognition #7-152 | The ClearLLab 10C panels when run on eachspecimen type by different operators ondifferent Navios EX flow cytometersdemonstrated acceptable precisionperformance and met acceptance criteria. |
| Clinical Accuracy | Evaluate the clinical accuracyof the ClearLLab 10C Panelsin identifying an abnormal ornormal phenotype vs. the | None | CLSI H43-A2: Clinical FlowCytometric Analysis of NeoplasticHematolymphoid Cells - Second | Analysis of the data collected demonstratesthat the ClearLLab 10C panels are able |
| Study | Objective | FDA Guidance Documents | Standards/ References | Testing Results |
| site's clinical diagnosis ofmalignant or non-malignantoutcome from the currentstandard of care | Edition; FDA StandardsRecognition #7-150User Protocol for Evaluation ofQualitative Test Performance;Approved Guideline – SecondEdition; CLSI EP12-A2; FDAStandards Recognition #7-152CLSI EP24-A2: Assessment of theDiagnostic Accuracy of LaboratoryTets Using Receiver OperatingCharacteristic Curves; ApprovedGuideline – Second Edition; FDAStandards Recognition #7-234 | identify the abnormal population whencompared to clinical outcome. | ||
| Study | Objective | FDA Guidance Documents | Standards/ References | Testing Results |
| IOTest 3 Fixative andIOTest 3 Lysing Solution -Lot-to-Lot Reproducibility | Demonstrate variability ofmultiple lots of material. | None | CLSI EP5-A3, Evaluation ofPrecision of QuantitativeMeasurement Procedures; ApprovedGuideline - Third Edition. FDAStandards Recognition #7-251 | Analysis of the data collected demonstratesthat the IOTest 3 Fixative and LysingSolutions have acceptable lot variabilityperformance. |
| Flow-Set Pro Lot-to-LotVariability | Demonstrate variability ofmultiple lots of material. | None | CLSI EP5-A3, Evaluation ofPrecision of QuantitativeMeasurement Procedures: ApprovedGuideline - Third Edition. FDAStandards Recognition #7-251 | Analysis of the data collected demonstratesthat the Flow-Set Pro have acceptable lotvariability performance. |
| Flow-Check Pro Lot-to-LotVariability | Demonstrate variability ofmultiple lots of material. | None | CLSI EP5-A3, Evaluation ofPrecision of QuantitativeMeasurement Procedures; ApprovedGuideline - Third Edition. FDAStandards Recognition #7-251 | Analysis of the data collected demonstratesthat the Flow-Check Pro have acceptable lotvariability performance. |
| ClearLLab CompensationKit with ClearLLabCompensation BeadsReagent Stability | Demonstrate reagentstability. | None | None | Analysis of the data collected demonstratesthat the Compensation Kit and CompensationBeads meet performance requirements insupport of the products' stability claims. |
| IOTest 3 Lysing Solutionand Fixative ReagentStability | Demonstrate reagentstability. | None | None | Analysis of the data collected demonstratesthat the IOTest 3 Fixative Solution andLysing Solutions meet performancerequirements in support of the product'sstability claims. |
| Flow-Set Pro FluorospheresReagent Stability | Demonstrate reagentstability. | None | CLSI EP25-A - Evaluation ofStability of In Vitro DiagnosticReagents. Approved Guideline:FDA Standards Recognition #7-235 | Analysis of the data collected demonstratesthat the Flow-Set Pro Fluorospheres meetperformance requirements in support of theproduct's stability claims. |
| Flow-Check ProFluorospheres ReagentStability | Demonstrate reagentstability. | None | CLSI EP25-A – Evaluation ofStability of In Vitro DiagnosticReagents. Approved Guideline:FDA Standards Recognition #7-235 | Analysis of the data collected demonstratesthat the Flow-Check Pro Fluorospheres meetperformance requirements in support of theproduct's stability claims. |
| Flow-Set Pro AnalyteValue Assignment | Define Flow-Set Pro Targetranges for use with theClearLLab 10C panels anddefine a process for rangestransfer from one lot of Flow-Set Pro Fluorospheres. | None | None | Analysis of the data collected demonstratesthat appropriate Flow-Set Pro target rangesare defined for use with the ClearLLab 10Cpanels and that a process for ranges transferfrom one lot of Flow-Set Pro Fluorospheresto another one is in place. |
Summary of Instrument Characterization and Analytical Performance Testing
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Summary of ClearLLab 10C Reagents (T, B, M1, M2) Performance Testing:
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Summary of Accessory Reagents Performance Testing:
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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.
§ 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.