(270 days)
The DxH 520 is a quantitative, multi-parameter, automated hematology analyzer for in vitro diagnostic use in clinical laboratories and physician's office laboratories. It is used to identify the normal patient with normal system-generated parameters from patients with abnormal parameters and/or flags that require additional studies.
The DxH 520 identifies and enumerates the following parameters: WBC, RBC, HGB, HCT, MCV, MCH, MCHC, RDW, RDW-SD, PLT, MPV, LY%, LY#, MO%, MO#, NE%, EO%, EO#, BA%, BA# in whole blood samples (venous and capillary) collected in K2EDTA and K3EDTA anticoagulants, and prediluted whole blood.
The instrument is for use in adult and pediatric populations, including neonates.
The DxH 520 instrument provides a complete blood count (CBC with Five Part Differential (5PD)). Blood specimens are processed using a Closed Vial sampling method as default and have the option to run as Open Vial per operator selection.
RBC, WBC and PLT cell counts and sizes are determined using the Coulter Principle (impedance). The WBC 5 part differential is determined using a combination of the impedance WBC data and the direct optical measurement (Axial Light Loss - ALL) using a blue LED focused through the WBC aperture. With the addition of the DxH 500 Series Lyse, the RBCs are lysed and the released hemoglobin is converted into stable Oxyhemoglobin (or Carboxyhemoglobin, if present). The resulting complex is then measured by spectrophotometry.
The data obtained from the counting, sizing, optical and hemoglobin measurements is processed to create the DxH 520 hematological measurement that the device reports. Raw information is digitized from all analytical modules and passed to an embedded computer processing. Algorithms using dynamic gates to differentiate WBC subpopulations and flagging are performed within the embedded computer.
Controls and calibrators are used to monitor the performance of the instrument.
The compact bench top design of the DxH 520 will benefit small laboratories where bench space is limited. The integrated color display with graphical icon based user interface is intended to facilitate ease of use and operator training. The small bench-top DxH 520 instrument utilizes fully featured integrated software usually found on larger instrumentation.
This document describes the premarket notification for the Beckman Coulter DxH 520 Hematology Instrument (K181475). The information provided is based on the "Performance Summary" table (Table 7) on pages 14-15 of the document.
1. Table of Acceptance Criteria and Reported Device Performance
| Study/Parameter | Acceptance Criteria/Guidance | Reported Device Performance |
|---|---|---|
| Measurement Procedure Comparison | Comparison to the predicate DxH800 for CBC and differential values (clinical and small lab/POL sites). Comparison to manual microscopy (reference method) for WBC differential. Relevant FDA Guidances: "Special Controls Guidance Document: Premarket Notifications for Automated Differential Cell Counters for Immature or Abnormal Blood Cells - Accuracy (Section 8)"; Relevant Standards: CLSI H26-A2, CLSI H20-A2, CLSI GP41-A6, CLSI GP42-A6. | The results support the accuracy claims for all parameters. The data showed substantial equivalency of the CBC and DIFF parameters to the DxH 800 predicate system at large clinical laboratories (including cancer centers) and at small laboratories with less experienced operators. The DxH 520 is substantially equivalent to the reference method (manual slides) for the differential proportional parameters. |
| Precision | Assessment of long-term precision (repeatability and reproducibility) for all parameters. All whole blood repeatability acceptance criteria were met. All pre-dilute repeatability parameters met all requirements. Relevant FDA Guidance: "Special Controls Guidance Document: Premarket Notifications for Automated Differential Cell Counters for Immature or Abnormal Blood Cells - Precision (Section 9)"; Relevant Standards: CLSI H26-A2, CLSI EP05-A3, CLSI H20-A2. | The long-term precision (repeatability and reproducibility) meets the requirements as specified for all parameters. All whole blood repeatability acceptance criteria for all parameters were met. All pre-dilute repeatability parameters met all requirements. The pre-dilute precision is highly dependent on the operator's preparation of the dilutions. The Operator to Operator Variability of pre-dilute and whole blood for between operator and within specimen are provided as performance characteristics only. The variability at small laboratories does not invalidate the results as the same users participated in the accuracy study where all specifications were met. The pre-analytical handling of samples in a POL setting provides accurate analysis on the DxH 520 and has low impact on operator variability. |
| Clinical Sensitivity (Flagging) | Assess clinical sensitivity and specificity of overall flagging on the DxH 520 compared to the accepted reference method for differential determination (manual slide counts). Relevant FDA Guidance: "Special Controls Guidance Document: Premarket Notifications for Automated Differential Cell Counters for Immature or Abnormal Blood Cells - Performance (Section 10)"; Relevant Standards: CLSI H26-A2, CLSI H20-A2, CLSI EP12-A2, CLSI GP41-A6, CLSI GP42-A6. | The false negative samples were reviewed by the Beckman Coulter Medical Director for their potential clinical impact. There were no false negatives generated by blasts in this data set. Based on the Medical Director assessment, none of the false negatives that occurred would have compromised patient diagnosis and treatment. The overall rate of FN was 13.5% with a sensitivity of 86.5% and specificity of 68.7%. |
| Linearity | Demonstrating that reported results are directly proportional to the measurand concentration for WBC, RBC, HGB, and PLT. Relevant FDA Guidance: "Special Controls Guidance Document: Premarket Notifications for Automated Differential Cell Counters for Immature or Abnormal Blood Cells - Linearity (Section 11)"; Relevant Standards: CLSI H26-A2, CLSI EP06-A. | The WBC, RBC, Hgb, and Plt parameters met the linearity specifications. |
| Carryover | Verification of carryover for WBC, RBC, HGB, and PLT. Relevant FDA Guidance: "Special Controls Guidance Document: Premarket Notifications for Automated Differential Cell Counters for Immature or Abnormal Blood Cells - Carryover (Section 12)"; Relevant Standard: CLSI H26-A2. | All carryover testing for WBC, differential, RBC, PLT, and Hgb met the specification with 95% confidence on the upper limit. |
| Detection Capability (LoB, LoD, LoQ) | Assess performance detection capability limits using precision profiles for Lower Limit of Detection (LLoD) and Lower Limit of Quantitation (LLoQ) for WBC, RBC, HGB, and PLT measurands. Relevant Standards: CLSI H26-A2, CLSI EP17-A2. | Results for the detection capability of each instrument for the WBC, RBC, Hgb, and Plt parameters were within the specifications. |
| Specimen Stability | Assess stability: long-term for drift over time at RT and refrigerated, and pre-dilute for drift over 90 minutes. Relevant Standards: CLSI H26-A2, CLSI EP25-A. | All parameters met the corresponding requirements for whole blood specimen stability at 8hrs and 24hrs. Results were within the specifications. All parameters met the corresponding requirements for Pre-dilute Stability claim of 15 minutes. |
| Interfering Substances | Determine the level of lipemia, bilirubin, leukocytes, and hemoglobin that affects hematology results. Relevant Standards: CLSI H26-A2, C56-A. | The concentrations indicated for Lipemia (62.5 mg/dl), Conjugated Bilirubin (40mg/dl), Unconjugated Bilirubin (20mg/dl), and Hemoglobin (200 mg/dl) are the highest concentrations that did not interfere with the CBC parameters. For Leucocytes (100 x10^3/uL), this is the highest concentration that did not interfere with the Hemoglobin parameter. |
| Equivalency | Demonstrate pre-analytical and within-instrument equivalency for Pre-Dilute vs. Whole Blood, K2 and K3 EDTA, and all sampling modes. Relevant Standard: CLSI H26-A2. | In all sampling modes, the results demonstrated equivalency for all parameters tested and performance was within the specifications of the instrument. |
| Reference Intervals | Establish reference intervals for adult males/females and pediatric (0 days - 21 years) males/females combined. Relevant FDA Guidance: "Special Controls Guidance Document: Premarket Notifications for Automated Differential Cell Counters for Immature or Abnormal Blood Cells - Reference Values (Section 14)"; Relevant Standard: EP28-A3c. | The adult reference interval was established on the DxH520 system for all parameters and included in the product labeling and software. |
2. Sample Size Used for the Test Set and Data Provenance
The document does not explicitly state the exact sample sizes for each test set within the "Performance Summary" table. However, it indicates:
- Measurement Procedure Comparison: Samples were collected from "clinical sites and small laboratory / physician office laboratory sites." This suggests prospective collection of real-world patient samples.
- Precision: Three studies were conducted:
- Long Term Precision: Clinical and Small Laboratory/POL Sites.
- Short term precision: Whole blood Repeatability.
- Short term precision: Pre-Dilute Repeatability.
Again, implying real-world or simulated patient samples.
- Clinical Sensitivity: Not directly specified, but false negative samples were reviewed.
- Other studies (Linearity, Carryover, Detection Capability, Specimen Stability, Interfering Substances, Equivalency): The description of these studies suggests the use of various control materials, diluted samples, and potentially spiked samples, rather than a broad range of patient samples.
Data Provenance: The studies for accuracy and precision were conducted at "clinical sites and small laboratory / physician office laboratory sites," indicating a mix of real-world clinical environments. The document does not specify the country of origin of the data, but it is a US FDA 510(k) submission, suggesting primarily US-based evaluation. The nature of the studies implies prospective data collection for validation tests.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
- Measurement Procedure Comparison (WBC Differential): The reference method used was "manual microscopy." While "experts" are inherently involved in manual microscopy for differential counts, the number of experts and their specific qualifications (e.g., "radiologist with 10 years of experience") are not explicitly stated in this document.
- Clinical Sensitivity (Flagging): "The false negative samples were reviewed by the Beckman Coulter Medical Director for their potential clinical impact." This indicates one expert (a Medical Director) was involved in reviewing clinical impact for false negatives. Their specific qualifications are not detailed beyond being a "Medical Director."
4. Adjudication Method for the Test Set
The document does not explicitly describe a formal adjudication method (like 2+1 or 3+1) for establishing ground truth for the test sets.
- For the measurement procedure comparison, the "manual microscopy" is presented as the reference method. It's implied this is the accepted ground truth for WBC differential without further adjudication details.
- For clinical sensitivity, the "Beckman Coulter Medical Director" reviewed false negative samples. This indicates a single expert review, not a consensus-based adjudication, specifically for the clinical impact of false negatives, not for establishing all ground truths.
5. If a Multi Reader Multi Case (MRMC) Comparative Effectiveness Study was Done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance
No. The DxH 520 is an automated hematology instrument, not an AI-assisted diagnostic tool that involves human readers interpreting images. The studies performed were to validate the performance of the automated instrument itself against predicate devices and reference methods. Therefore, an MRMC comparative effectiveness study involving human reader improvement with/without AI assistance is not applicable and was not performed.
6. If a Standalone (i.e. algorithm only without human-in-the-loop performance) was Done
Yes. The entire submission for the DxH 520 Hematology Instrument is focused on its standalone performance as an automated analyzer. The "Measurement Procedure Comparison" directly compares the device's numerical results to a predicate device and manual microscopy, demonstrating its performance without human intervention in the primary measurement. The "Clinical Sensitivity" study evaluates the device's flagging algorithm performance alone.
7. The Type of Ground Truth Used
The types of ground truth used include:
- Expert Consensus (implied): "Manual microscopy" for WBC differential is considered the reference method and implicitly involves expert interpretation.
- Predicate Device Data: For CBC and differential values, the predicate DxH 800 served as a comparative ground truth to establish substantial equivalence.
- Pre-defined Specifications/Standards: For linearity, carryover, detection capability, stability, and interfering substances, the ground truth is established by recognized standards (e.g., CLSI guidelines) or internal specifications against which the device's measurements are assessed.
- Medical Director Review: For assessment of clinical impact of false negatives, a Medical Director's review served as a form of expert-determined ground truth for clinical relevance.
8. The Sample Size for the Training Set
The document does not provide information regarding a "training set" or its sample size. This is typical for an instrument validation submission of this nature where the focus is on the performance of a fully developed device, rather than the development and training of a machine learning algorithm. The "algorithms using dynamic gates to differentiate WBC subpopulations and flagging" are mentioned as being performed within the embedded computer, but details of their development or training data are not included in this summary.
9. How the Ground Truth for the Training Set Was Established
Since no information on a "training set" is provided, the method for establishing its ground truth is also not available in this document.
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Image /page/0/Picture/0 description: The image shows the logos of the Department of Health & Human Services and the Food and Drug Administration (FDA). The Department of Health & Human Services logo is on the left, and the FDA logo is on the right. The FDA logo includes the text "FDA U.S. FOOD & DRUG ADMINISTRATION" in blue.
April 23, 2019
Beckman Coulter Samy Puccio Staff Regulatory Affair Specialist 11800 SW 147th Ave Miami, Florida 33196-2500
Re: K181475
Trade/Device Name: DxH 520 Hematology Instrument Regulation Number: 21 CFR 864.5220 Regulation Name: Automated differential cell counter Regulatory Class: Class II Product Code: GKZ Dated: June 1, 2018 Received: June 4, 2018
Dear Samy Puccio:
This letter corrects our substantially equivalent letter of March 1, 2019.
We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent for the indications for use stated in the enclosure to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food, Drug, and Cosmetic Act (Act) that do not require approval of a premarket approval application (PMA). You may, therefore, market the device, subject to the general controls provisions of the Act and the limitations described below. Although this letter refers to your product as a device, please be aware 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.
The Office of In Vitro Diagnostics and Radiological Health has determined that there is a reasonable likelihood that this device will be used for an intended use not identified in the proposed labeling and that such use could cause harm. Therefore, in accordance with Section 513(i)(1)(E) of the Act, the following limitation must appear in the Intended Use statement of the device's labeling:
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All numerical results reported for Basophil count and percent values must be reflexed for manual microscopy or followed up for additional testing based on the laboratory's SOP.
Furthermore, the intended use/indication for use:
The DxH 520 is a quantitative, multi-parameter, automated hematology analyzer for in vitro diagnostic use in clinical laboratories and physician's office laboratories. It is used to identify the normal patient with normal system-generated parameters from patients with abnormal parameters and/or flags that require additional studies.
The DxH 520 identifies and enumerates the following parameters: WBC, RBC, HGB, HCT, MCH, MCHC, RDW, RDW-SD, PLT, MPV, LY%, LY#, MO%, MO#, NE%, NE#, EO%, EO#, BA%, BA# in whole blood samples (venous and capillary) collected in K2EDTA and K3EDTA anticoagulants, and prediluted whole blood.
The instrument is for use in adult and pediatric populations, including neonates.
must be prominently displayed in all labeling, including pouch box, and carton labels, instructions for use, and other promotional materials, in close proximity to the trade name, of a similar point size, and in bold print.
Please note that the above labeling limitations are required by Section 513(i)(1)(E) of the Act. Therefore, a new 510(k) is required before these limitations are modified in any way or removed from the device's labeling.
The FDA finding of substantial equivalence of your device to a legally marketed predicate device results in a classification for your device and permits your device to proceed to the market. This letter will allow you to begin marketing your device as described in your Section 510(k) premarket notification if the limitation statement described above is added to your labeling.
If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. In addition, FDA may publish further announcements concerning your device in the Federal Register.
Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR 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.html; 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.
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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 mediation-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,
Timothy T. Stenzel -S
Timothy Stenzel, MD, PhD Director Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health
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Indications for Use
510(k) Number (if known) K181475
Device Name DxH 520 Hematology Instrument
Indications for Use (Describe)
The DxH 520 is a quantitative, multi-parameter, automated hematology analyzer for in vitro diagnostic use in clinical laboratories and physician's office laboratories. It is used to identify the normal patient with normal system-generated parameters from patients with abnormal parameters and/or flags that require additional studies.
The DxH 520 identifies and enumerates the following parameters: WBC, RBC, HCT, MCV, MCH, MCHC, RDW, RDW-SD, PLT, MPV, LY%, LY#, MO%, MO#, NE%, NE#, EO%, BA# in whole blood samples (venous and capillary) collected in K2EDTA and K3EDTA anticoagulants, and prediluted whole blood.
The instrument is for use in adult and pediatric populations, including neonates.
LIMITATIONS
All numerical results reported for Basophil count and be reflexed for manual microscopy or followed up for additional testing based on the laboratory's SOP.
| 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) |
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DxH 520
Section 5
510(k) Summary
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510(k) Summary for DxH 520 Hematology Instrument
510(k) Owner / Submitter Information
Name: Beckman Coulter Inc. Address: 11800 SW 147th Ave., Miami, FL 33196 Phone #: (305) 380-4509 Fax #: (786) 639-2584 Contact Person: Samy Puccio Email Address: spuccio@beckman.com
Date Submitted: June 1, 2018
Device Name and Classification
Trade Name: DxH 520 Hematology Instrument Common Name: DxH 520 Classification: Class II Classification Name: Automated differential cell counter (21 CFR 864.5220) Product Code: GKZ Panel: Hematology
Predicate Device Information
| Predicate Product | 510(k)Number | DateCleared | Classification | 21 CFR | ProductCode |
|---|---|---|---|---|---|
| UniCel® DxH 800Coulter® CellularAnalysis System | K140911 | 09/05/2014 | Class II | 864.5220 | GKZ |
| Manually preparedblood films perthe manual wedge-pull film technique asdescribed in CLSIH20-A2, ReferenceLeukocyte (WBC)Differential Count(Proportional) andEvaluation ofInstrument Methods;Approved Standard –Second Edition | N/A | N/A | N/A | N/A | N/A |
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Device Description
The DxH 520 instrument provides a complete blood count (CBC with Five Part Differential (5PD)). Blood specimens are processed using a Closed Vial sampling method as default and have the option to run as Open Vial per operator selection.
Image /page/6/Picture/2 description: The image shows a medical device, specifically a hematology analyzer, which is used for counting and characterizing blood cells. The device has a screen displaying an image of blood cells, and the name "DxH 520" is visible on the front. A barcode scanner is connected to the device, and there is a slot for inserting samples for analysis.
RBC, WBC and PLT cell counts and sizes are determined using the Coulter Principle (impedance). The WBC 5 part differential is determined using a combination of the impedance WBC data and the direct optical measurement (Axial Light Loss - ALL) using a blue LED focused through the WBC aperture. With the addition of the DxH 500 Series Lyse, the RBCs are lysed and the released hemoglobin is converted into stable Oxyhemoglobin (or Carboxyhemoglobin, if present). The resulting complex is then measured by spectrophotometry.
The data obtained from the counting, sizing, optical and hemoglobin measurements is processed to create the DxH 520 hematological measurement that the device reports. Raw information is digitized from all
analytical modules and passed to an embedded computer processing. Algorithms using dynamic gates to differentiate WBC subpopulations and flagging are performed within the embedded computer.
Controls and calibrators are used to monitor the performance of the instrument.
The compact bench top design of the DxH 520 will benefit small laboratories where bench space is limited. The integrated color display with graphical icon based user interface is intended to facilitate ease of use and operator training. The small bench-top DxH 520 instrument utilizes fully featured integrated software usually found on larger instrumentation.
Intended use
The DxH 520 is a quantitative, multi-parameter, automated hematology analyzer for in vitro diagnostic use in clinical laboratories and physician's office laboratories. It is used to identify the normal patient with normal system-generated parameters from patients with abnormal parameters and/or flags that require additional studies.
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The DxH 520 identifies and enumerates the following parameters: WBC, RBC, HGB, HCT, MCV, MCH, MCHC, RDW, RDW-SD, PLT, MPV, LY%, LY#, MO%, MO#, NE%, EO%, EO#, BA%, BA# in whole blood samples (venous and capillary) collected in K2EDTA and K3EDTA anticoagulants, and prediluted whole blood.
The instrument is for use in adult and pediatric populations, including neonates.
LIMITATIONS
All numerical results reported for Basophil count and percent values must be reflexed for manual microscopy or followed up for additional testing based on the laboratory's SOP.
Technological Characteristics Comparisons to Predicate
The tables below describe the similarities and differences between the predicate device, the DxH 800 Cellular Analysis System, and the DxH 520 Hematology Instrument.
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| Characteristic | UniCel DxH800Predicate | DxH 520 | Similarity / Difference |
|---|---|---|---|
| Intended Useand Function | The UniCel® DxH 800 Analyzer is a quantitativemulti-parameter, automated hematology analyzerfor in vitro diagnostic use in screening patientpopulations found in clinical laboratories.The UniCel® DxH 800 Analyzer identifies andenumerates the parameters indicated below on thefollowing sample types:Whole Blood (Venous and Capillary) WBC, RBC, HGB, HCT, MCV,MCH, MCHC, RDW, RDW-SD,PLT, MPV, NE%, NE#, LY%, LY#,MO%, MO#, EO%, EO#, BA%,BA#, NRBC%, NRBC#, RET%,RET#, MRV, IRF Pre-Diluted Whole Blood (Venous andCapillary) WBC, RBC, HGB, HCT, MCV,MCH, MCHC, RDW, RDW-SD,PLT, MPV Body Fluids (cerebrospinal, serous andsynovial) TNC and RBC | The DxH 520 is a quantitative, multi-parameter,automated hematology analyzer for in vitrodiagnostic use in clinical laboratories; includinghospital, reference, and physician's officelaboratories. It is used to identify the normal patientwith normal system-generated parameters frompatients with abnormal parameters and/or flags thatrequire additional studies.The DxH 520 Analyzer identifies and enumeratesthe measurands listed below on the followingsample types: Whole Blood (Venous and Capillary) WBC, RBC, HGB, HCT, MCV,MCH, MCHC, RDW, RDW-SD,PLT, MPV, NE%, NE#, LY%,LY#, MO%, MO#, EO%, EO#,BA%, BA# Pre-Diluted Whole Blood (Venous andCapillary) WBC, RBC, HGB, HCT, MCV,MCH, MCHC, RDW, RDW-SD,PLT, MPV, NE%, NE#, LY%,LY#, MO%, MO#, EO%, EO#,BA%, BA# The instrument is for use in adult and pediatricpopulations, including neonates.LIMITATIONSAll numerical results reported for Basophil countand percent values must be reflexed for manualmicroscopy or followed up for additional testingbased on the laboratory's SOP. | The indications for use statements arethesame for the CBC and 5 part differentialAnalysis measurands.By design, the DxH 520 does notenumerate Reticulocytes or NRBC onwholeblood, nor perform analysis of BodyFluidspecimens.By design, the DxH 520 enumeratesWBC differential measurands onpredilutesample types while the predicatedoes not. |
Table 1 - Intended Use and Function Similarities
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| Characteristic | UniCel DxH800Predicate | DxH 520 | Similarity / Difference | |
|---|---|---|---|---|
| Principles of Measurement | ||||
| WBC, RBC, MCV,Platelet | Aperture impedance (Coulter® Principle) | Aperture impedance (Coulter® Principle) | Same as predicate | |
| Hemoglobin | Spectrophotometric | Spectrophotometric | Same as predicate | |
| WBC Differential | VCSn Technology using :• Aperture impedance (DC)• Conductivity (RF)• Laser Light Scatter (Multipleangles)• Laser Light Absorbance | Optical / Impedance• Aperture impedance (DC)• Light Absorbance (LED) -Axial LightLost | The measurement methods of the DxH520 are similar to the predicate.The DxH 520 only uses impedanceand Light absorbance in the WBCDifferential measure. The light sourcefor the optical method is an LEDThe light source for DxH 800 optical is aLaser | |
| Reticulocytes | VCSn Technology using :• Aperture impedance (DC)• Conductivity (RF)• Laser Light Scatter (Multipleangles)• Laser Light Absorbance | N/A | DxH 520 does not enumerateReticulocytes | |
| NRBC | VCSn Technology using :• Aperture impedance (DC)• Conductivity (RF)• Laser Light Scatter (Multipleangles)• Laser Light Absorbance | N/A | DxH 520 does not enumerateReticulocytes |
Table 2 - Principles of Measurement Similarities
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Table 3 - Reagents Similarities
| Characteristic | UniCel DxH800Predicate | DxH 520 | Similarity / Difference |
|---|---|---|---|
| Reagents | |||
| AnalysisReagents | COULTER® DxH DiluentCOULTER® DxH Diff PackCOULTER® DxH Cell LyseCOULTER® DxH Retic PackCOULTER® DxH Cleaner | DxH 500 Series DiluentDxH 500 Series LyseDxH 500 Series Cleaner | Coulter DxH Diluent and DxH 500 SeriesDiluent have different formulation.DxH 500 Series Lyse performs the functionsof DxH Diff Pack and DxH Cell Lyse, i.e.lyse RBC's, convert HGB to stable pigmentand maintain WBC's for counting anddifferential analysis.COULTER® DxH Cleaner and DxH 500Series Cleaner have the same formulationDxH Retic- N/A since DxH 520 does notenumerate reticulocytes |
| Quality Controls& Calibrator | COULTER 6C Cell ControlCOULTER Latron™ CP-X ControlCOULTER RETIC-X Cell ControlCOULTER LIN-X ControlCOULTER Body Fluids ControlCOULTER S-CAL® Calibrator kit | DxH 500 Series ControlDxH 500 Series CalibratorDxH 500 Linearity Kit | The control and calibrator products both usehuman and animal cells to simulate humancell populations; each product is optimizedfor the reagents and technology used.Linearity products both use human andanimal cells to simulate human cellpopulations.DxH 520 does not require productsequivalent to the Latron, Retic and BodyFluids controls.DxH 520 cell control, calibrator and linearitykit will have the same intended use as theDxH products. |
| Table 4 - Pre-Analytical Features Similarities | |||
| Characteristic | UniCel DxH800Predicate | DxH 520 | Similarity / Difference |
| Pre-Analytic Features | |||
| Systemconfiguration | Bench top or Optional Floor Stand -provides self-contained support for theanalyzer as well as easy access storagefor reagents and waste containersPC based workstation running MicrosoftWindows XP application specificsoftwareHandheld Barcode ScannerPrinter | Bench top onlyIntegrated single board computer with color touchscreen running application specific software usingLinux OSHandheld Barcode ScannerPrinter | Similar to predicate for the systemconfiguration of benchtop, barcode scannerand printerDifferent operating systems |
| SamplingMechanism | Single tube presentation - open and closed vialsampling.Automated presentation - closed vial samplingfrom 5 position cassette; Maximum initial loadcapacity 20 racks | Single tube manual open and closed vial | DxH 520 does not provide Automatedpresentation |
| Mechanisms forprocessing | Mechanisms to achieve process of :Automated cassette transportation and specimenmixing (by rocking), sample aspiration, samplepreparation, sample and reagent presentation toanalytical modules, sample analysis, raw datacollection, algorithmic processing and datareporting.Cassette transportation by magnetic drive allowingmulti-directional moves and capability to returncassette toSampling position for repeat / reflex testing. | Manual specimen mixing and presentation to theanalyzer, user initiated sample aspiration followedby automatic sample preparation through sampleand reagent deliveryto the analytical modules, followed by datacollection, algorithmic processing and datareporting | DxH 520 provides manual open and closedvialmechanisms for processing whilepredicate provides additionalautomated and closed vial sampling |
| Sampleidentification | Sample aspiration module (SAM) mountedbarcode reader for automated barcode reading ofcassette and sample tube identifiers Manualbarcode scanning of sample tube identifier(Handheld scanner) Manual keyboard entry ofsample identifier | Manual barcode scanning of sample tube identifier(Handheld scanner) Manual keyboard entry ofsampleidentifier | Automated: DxH 520 does not haveautomated sample identification mechanismsManual sample identification same aspredicate |
| Characteristic | UniCel DxH800Predicate | DxH 520 | Similarity / Difference |
| Sample Processing | |||
| AspirationPathway | Single sampling probe and common aspirationpathway used for all sample presentation modes. | Single sampling probe for open and closed vialprocessing and single aspiration pathway. | DxH 520 has open and closed sampling modewith single aspiration pathway. |
| Sampleaspirationvolume | Automatic, cap-piercing : 165 μLSingle tube - open-vial and cap pierce:165 μL | Single tube - open and closed vial 16.7 μL | DxH 520 aspirates the same volume for openand closed vial |
| Pre-dilute 165 μL - fixed ratio of 1 in 5 dilution ofblood with diluent | Pre-dilute 20μL whole blood + 300 μL diluent | ||
| Throughput | Automated cassette processing-CBC ≥100 specimens per hourCBC/Diff≥100 specimens per hourCBC/Diff/NRBC ≥ 90 specimens per hourAny cycle with Retic ≥45 specimens perhour(Throughput is based on normal specimens -analytical cycle times are increased with cytopenicspecimens) | 55 Samples per hour in CP mode60 Samples per hour in OV mode | Different throughput and processing typesand rates for the DxH 520 and predicate |
| Data reporting | Workstation display graphics, hardcopyprinting and transmission to LaboratoryInformation System (LIS) | Display of graphics, hardcopy printing andtransmission toLaboratory Information System (LIS) | Same as predicate |
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Table 4 - Pre-Analytical Features Similarities
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Table 5 - Sample Processing Similarities
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| UniCel DxH800Predicate | DxH 520 | Similarity / Difference | |
|---|---|---|---|
| Characteristic | System Control | ||
| Controllingsoftware | System software (embedded and workstation)designed specific tosupport all features of DxH 800. The softwaresystem consists of a Data Manager component, aSystem Manager component (includingalgorithms), the User Interface, all of which areresident in the Workstation.In addition an Embedded Application is resident inthe analyzer. The Embedded application uploadsfrom theworkstation on system power-up.Extensive realtime monitoring and reporting of system statusincluding:Component and module activities,System Voltages and Currents System Pressure and Vacuum System Temperatures Motor activity Mechanism Sensor status Reagent Pump Operation Raw data collectionSingle samplingprobe and common aspiration pathwayused for all sample presentation modes. | System software designed specific to support allfeatures of DxH 520 and DxH 500.The Software runs on an integrated single boardcomputer with color touch screen using Linux OS.Software provides all functions required for theUser Interface, Data analysis, Results management,Instrument control and monitoring | DxH 520 software is designed witharchitecture to provide similar functions andcapability as the DxH 800 within the DxH520 design and architecture. |
Table 6 - System Control Similarities
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| STUDY | TESTING APPROACH | FDA GUIDANCEDOCUMENTS | STANDARDS/REFERENCES | TESTING RESULTS |
|---|---|---|---|---|
| Measurement ProcedureComparison | To compare the results (CBCand differential values) fromtest instruments versus thepredicate DxH800 at clinicalsites and small laboratory /physician office laboratorysites.Comparison to manualmicroscopy as the referencemethod was performed for theWBC differential on the DxH520 | Special Controls GuidanceDocument: PremarketNotifications for AutomatedDifferential Cell Countersfor Immature or AbnormalBlood Cells - Accuracy(Section 8) | CLSI H26-A2 ValidationVerification and QualityAssurance of AutomatedHematology Analyzers - June2010. FDA StandardsRecognition # 7-210CLSI H20-A2 ReferenceLeukocyte (WBC) DifferentialCount (Proportional) andEvaluation of InstrumentalMethods; Approved standard -Second Edition January 2007.FDA Standards Recognition #7-165CLSI GP41-A6 Procedures forthe Collection of DiagnosticBlood Specimens byVenipuncture; ApprovedStandard-Sixth Edition. October2007. FDA StandardsRecognition # 7-201CLSI GP42-A6 Procedures andDevices for the Collection ofDiagnostic Capillary BloodSpecimens; Approved Standard-Sixth Edition. September 2008.FDA Standards Recognition # 7-203 | The results support theaccuracy claims for allparameters. The datapresented showssubstantial equivalency ofthe CBC and DIFFparameters to the DxH 800predicate system at largeclinical laboratories thatinclude cancer centers, andat small laboratories withless experienced operators.The DxH 520 issubstantially equivalent tothe reference method(manual slides) for thedifferential proportionalparameters. |
| Precision | To assess precision of the DxH520, three (3) studies wereconducted: | Special Controls GuidanceDocument: PremarketNotifications for AutomatedDifferential Cell Countersfor Immature or AbnormalBlood Cells - Precision | CLSI H26-A2 ValidationVerification and QualityAssurance of AutomatedHematology Analyzers - June2010. FDA StandardsRecognition # 7-210 | The long term precision(repeatability andreproducibility) meets therequirements as specifiedfor all parameters |
| STUDY | TESTING APPROACH | FDA GUIDANCEDOCUMENTS | STANDARDS/REFERENCES | TESTING RESULTS |
| Long Term Precision - Clinicaland Small Laboratory/POLSites,Short term precision – Wholeblood Repeatability,Short term precision - Pre-Dilute Repeatability. | (Section 9) | CLSI EP05-A3 Evaluation ofPrecision QuantitativeMeasurement Procedures-ThirdEdition. September 2014. FDAStandards Recognition # 7-251CLSI H20-A2 ReferenceLeukocyte (WBC) DifferentialCount (Proportional) andEvaluation of InstrumentalMethods; Approved standard -Second Edition January 2007.FDA Standards Recognition #7-165 | All whole bloodrepeatability acceptancecriteria for all parameterswere met.All pre-dilute repeatabilityparameters met allrequirements. The pre-dilute precision is highlydependent on theoperator's preparation ofthe dilutions. | |
| Precision | To assess operator to operatorvariability testing in both wholeblood and pre-dilute modes atphysician office laboratories orsmall laboratories with multipleoperators. | Special Controls GuidanceDocument: PremarketNotifications for AutomatedDifferential Cell Countersfor Immature or AbnormalBlood Cells - Precision(Section 9) | No applicable standards. | The Operator to OperatorVariability of pre-diluteand whole blood forbetween operator andwithin specimen areprovided as performancecharacteristics only. Thevariability at smalllaboratories does notinvalidate the results putforth by the instrument asthe same users participatedin the accuracy studywhere all specificationswere met. The pre-analytical handling ofsamples in a POL settingprovides accurate analysison the DxH 520 and haslow impact on operatorvariability. |
| Clinical Sensitivity | To assess the clinical sensitivityand specificity of the overall | Special Controls GuidanceDocument: Premarket | CLSI H26-A2 ValidationVerification and Quality | The false negative sampleswere reviewed by the |
| STUDY | TESTING APPROACH | FDA GUIDANCEDOCUMENTS | STANDARDS/REFERENCES | TESTING RESULTS |
| flagging on the DxH 520 ascompared to the acceptedreference method fordifferential determination,(manual slide counts). | Notifications for AutomatedDifferential Cell Countersfor Immature or AbnormalBlood Cells - Performance(Section 10) | Assurance of AutomatedHematology Analyzers - June2010. FDA StandardsRecognition # 7-210CLSI H20-A2 ReferenceLeukocyte (WBC) DifferentialCount (Proportional) andEvaluation of InstrumentalMethods; Approved standard -Second Edition January 2007.FDA Standards Recognition #7-165CLSI EP12-A2 User Protocol forEvaluation of Qualitative TestPerformance, ApprovedGuideline – 2nd Edition. FDAStandards Recognition # 7-152CLSI GP41-A6 Procedures forthe Collection of DiagnosticBlood Specimens byVenipuncture; ApprovedStandard-Sixth Edition. October2007. FDA StandardsRecognition # 7-201CLSI GP42-A6 Procedures andDevices for the Collection ofDiagnostic Capillary BloodSpecimens; Approved Standard-Sixth Edition. September 2008.FDA Standards Recognition # 7-203 | Beckman Coulter MedicalDirector for their potentialclinical impact. There wereno FN's generated byblasts in this data set.Based on the MedicalDirector assessment noneof the false negatives thatoccurred would havecompromised patientdiagnosis and treatment.The overall rate of FN was13.5% with a sensitivity of86.5% and specificity of68.7%. | |
| Linearity | Demonstrating that the reportedresults are directly proportionalto the concentration of the | Special Controls GuidanceDocument: PremarketNotifications for | CLSI H26-A2 ValidationVerification and QualityAssurance of Automated | The WBC, RBC Hgb andPlt parameters met thelinearity specifications. |
| STUDY | TESTING APPROACH | FDA GUIDANCEDOCUMENTS | STANDARDS/REFERENCES | TESTING RESULTS |
| measurand in a test sample forWBC, RBC, HGB, and PLT. | Automated DifferentialCell Counters forImmature or AbnormalBlood Cells - Linearity(Section 11) | Hematology Analyzers - June2010. FDA StandardsRecognition # 7-210CLSI EP06-A, Evaluation of theLinearity of QuantitativeMeasurement Procedures: AStatistical Approach; 1st Edition.FDA Standards Recognition # 7-193 | ||
| Carryover | To verify carryover. Testingwill be performed for WBC,RBC, HGB, and PLT only. | Special Controls GuidanceDocument: PremarketNotifications for AutomatedDifferential Cell Countersfor Immature or AbnormalBlood Cells - Carryover(Section 12) | CLSI H26-A2 ValidationVerification and QualityAssurance of AutomatedHematology Analyzers - June2010. FDA StandardsRecognition # 7-210 | All carryover testing forWBC, differential, RBC,PLT and Hgb meet thespecification with 95%confidence on the upperlimit. |
| Detection Capability(Limit Of Blank,Detection AndQuantitation) | To assess performancedetection capability limits usingprecision profiles for LowerLimit of Detection (LLoD) andLower Limit of Quantitation(LLOQ) for WBC, RBC, HGBand PLT measurands. | None | CLSI H26-A2 ValidationVerification and QualityAssurance of AutomatedHematology Analyzers - June2010. FDA StandardsRecognition # 7-210CLSI EP17-A2 Evaluation ofDetection Capability for ClinicalLaboratory measurementProcedures; Approved Guideline-second Edition. June 2012. FDAStandards Recognition #7-233 | Results for the detectioncapability of eachinstrument for the WBC,RBC, Hgb and Pltparameters were within thespecifications. |
| Specimen Stability | To assess specimen stability,two studies were conducted:Long term specimen stabilityassessed the drift in samplevalue over time at controlledroom temperature and atrefrigerated temperature. | None | CLSI H26-A2 ValidationVerification and QualityAssurance of AutomatedHematology Analyzers - June2010. FDA StandardsRecognition # 7-210 | All parameters met thecorrespondingrequirements for wholeblood specimen stability at8hrs and 24hrs. Resultswere within thespecifications. |
| STUDY | TESTING APPROACH | FDA GUIDANCEDOCUMENTS | STANDARDS/REFERENCES | TESTING RESULTS |
| Pre-dilute test case willdetermine the drift in dilutedsamples over 90 minutes. | CLSI EP25-A Evaluation ofStability of In Vitro DiagnosticReagents, 1st Edition. FDAStandards Recognition # 7-235 | All parameters met thecorrespondingrequirements for Pre-diluteStability claim of 15minutes. | ||
| Interfering Substances | To determine the level oflipemia, bilirubin, leukocytesand hemoglobin that affectshematology results on the DxH520. | None | CLSI H26-A2 ValidationVerification and QualityAssurance of AutomatedHematology Analyzers - June2010. FDA StandardsRecognition # 7-210C56-A Hemolysis, Icterus, andLipemia/Turbidity Indices asIndicators of Interference inClinical Laboratory Analysis;Approved Guideline July 2012.FDA Standards Recognition # 7-242 | The concentrationsindicated for Lipemia,Conjugated Bilirubin,Unconjugated Bilirubinand Hemoglobin are thehighest concentrations thatdid not interfere with theCBC parameters. ForLeucocytes, this is thehighest concentration thatdid not interfere with theHemoglobin parameter.Lipemia: 62.5 mg/dlConjugated Bilirubin:40mg/dlUnconjugated Bilirubin:20mg/dlHemoglobin: 200 mg/dlLeucocytes:100 x103/uL |
| Equivalency | To demonstrate pre-analyticaland within instrumentequivalency, three (3) studieswere performed:Pre-Dilute vs. Whole BloodSampling Modes | None | CLSI H26-A2 ValidationVerification and QualityAssurance of AutomatedHematology Analyzers - June2010. FDA StandardsRecognition # 7-210 | In all sampling modes, theresults demonstratedequivalency for allparameters tested andperformance was withinthe specifications of theinstrument. |
| K2 and K3 EDTAanticoagulant tube types and | CLSI GP41-A6 Procedures forthe Collection of Diagnostic | |||
| STUDY | TESTING APPROACH | FDA GUIDANCEDOCUMENTS | STANDARDS/REFERENCES | TESTING RESULTS |
| site of draw (venous orcapillary)All sampling modes (CapPierce, Open Vial and TubeHolder Open Vial) | Blood Specimens byVenipuncture; ApprovedStandard-Sixth Edition. October2007. FDA StandardsRecognition # 7-201CLSI GP42-A6 Procedures andDevices for the Collection ofDiagnostic Capillary BloodSpecimens; Approved Standard-Sixth Edition. September 2008.FDA Standards Recognition # 7-203 | |||
| Reference Intervals | To establish the referenceinterval for adult males andadult females. Also establishthe pediatric reference intervalfor males and femalescombined age 0 days - 21years. | Special Controls GuidanceDocument: PremarketNotifications forAutomated DifferentialCell Counters forImmature or AbnormalBlood Cells - ReferenceValues (Section 14) | EP28-A3c, Defining,Establishing, and VerifyingReference Intervals in theClinical Laboratory; ApprovedGuideline - Third Edition.October 2010. FDA StandardsRecognition # 7-224 | The adult referenceinterval was established onthe DxH520 system for allparameters and included inthe product labeling andsoftware. |
Table 7 – Performance Summary
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§ 864.5220 Automated differential cell counter.
(a)
Identification. An automated differential cell counter is a device used to identify one or more of the formed elements of the blood. The device may also have the capability to flag, count, or classify immature or abnormal hematopoietic cells of the blood, bone marrow, or other body fluids. These devices may combine an electronic particle counting method, optical method, or a flow cytometric method utilizing monoclonal CD (cluster designation) markers. The device includes accessory CD markers.(b)
Classification. Class II (special controls). The special control for this device is the FDA document entitled “Class II Special Controls Guidance Document: Premarket Notifications for Automated Differential Cell Counters for Immature or Abnormal Blood Cells; Final Guidance for Industry and FDA.”