(273 days)
No
The summary describes a quantitative measurement (MDW) derived from a hematology analyzer. While it uses a cut-off value for interpretation, there is no mention of AI or ML algorithms being used to calculate MDW or interpret the results. The performance study focuses on the clinical accuracy of the MDW parameter itself, not on the performance of an AI/ML model.
No
This device is an in vitro diagnostic (IVD) device used for quantitative measurement and aiding in the identification of patients with sepsis. It is not used for treating or preventing disease.
Yes
Explanation: The device is described as "designed for in vitro diagnostic use in screening patient populations by clinical laboratories" and measures Monocyte Distribution Width (MDW) which "aids in identifying patients with sepsis or at increased risk of developing sepsis." This directly aligns with the definition of a diagnostic device.
No
The device description explicitly states that the Early Sepsis Indicator requires the use of the UniCel DxH 800 Coulter Cellular Analysis System, which is described as a quantitative, automated hematology analyzer with both analyzer and workstation components. This indicates the device is a system that includes hardware, not solely software.
Yes, this device is an IVD (In Vitro Diagnostic).
Here's why:
- Intended Use: The intended use explicitly states it's for the "quantitative measurement of Monocyte Distribution Width (MDW)" from a "whole-blood venous sample." This involves analyzing a biological sample outside of the body to provide information about a patient's health status.
- Device Description: The device is described as a "quantitative, automated hematology analyzer (DxH 800) designed for in vitro diagnostic use in screening patient populations by clinical laboratories." This directly states its intended use as an in vitro diagnostic device.
- Regulatory Context: The device description mentions it was last cleared under a 510(k) (K140911), which is the regulatory pathway for many IVD devices in the United States. The current submission is also a 510(k).
- Clinical Use: The device is used to aid in identifying patients with sepsis or at increased risk of developing sepsis, which is a diagnostic purpose.
- Sample Type: It analyzes whole blood, a biological sample.
All of these points align with the definition and characteristics of an In Vitro Diagnostic device.
N/A
Intended Use / Indications for Use
The Unicel DxH 800 Coulter Cellular Analysis System with Early Sepsis Indicator Application is the quantitative measurement of Monocyte Distribution Width (MDW). The Early Sepsis Indicator is intended for use with adult patients presenting to the emergency department, on whom a white cell differential test has been ordered.
MDW is measured from a (K2EDTA) whole-blood venous sample within 2 hours of collection. MDW values greater than 20.0 together with other laboratory findings and clinical information, aids in identifying patients with sepsis or at increased risk of developing sepsis within the first 12 hours of hospital admission.
MDW values greater than 20.0 should be interpreted in association with other clinical information and diagnostic testing, as a proportion of patients without sepsis may have an elevated MDW value at baseline.
MDW values less than or equal to 20.0 cannot rule out sepsis or the development of sepsis within 12 hours of hospital admission. The Early Sepsis Indicator should not be used as the sole basis to determine the absence of sepsis.
The predictive value of the Early Sepsis Indicator for identifying sepsis in patients with hematological abnormalities has not been established.
Product codes (comma separated list FDA assigned to the subject device)
QFS, GKZ
Device Description
The Early Sepsis Indicator (ESI) requires the use of the UniCel DxH 800 Coulter Cellular Analysis System (DxH 800) and its reagents, controls and calibrators last cleared under 510(k) K140911.
The UniCel DxH 800 Coulter Cellular Analysis System contains a quantitative, automated hematology analyzer (DxH 800) designed for in vitro diagnostic use in screening patient populations by clinical laboratories. The system provides a Complete Blood Count (CBC), Leukocyte 5 Part Differential (Diff), Reticulocyte (Retic), Nucleated Red Blood Cell (NRBC) on whole blood, as well as, Total Nucleated Count (TNC), and Red Cell Count (RBC) on Body Fluids (cerebrospinal, serous and synovial). This submission adds a new parameter, Monocyte Distribution Width (MDW) to those mentioned above. This parameter has been shown to aid in the early detection of Sepsis in emergency room patients.
The system consists of two primary components, the workstation and the DxH 800 analyzer as shown in Figure 1. DxH 800 System Configuration. The primary function of the DxH 800 analyzer is to process samples and provide results to the workstation. The primary functions of the workstation are: user interface, system control, results processing and storage and external communications. The analyzer runs embedded code and the workstation runs Microsoft Windows 7 Operating System (OS).
Optionally, the workstation can be connected to:
- A printer for creating reports:
- A Laboratory Information System (LIS) for receiving test orders and releasing results; and
- Pro-Service Remote Management System (RMS) which provides secure access to the DxH800 workstation for BCI Service Personnel to perform troubleshooting, system monitoring and for assisting customers.
The version of the system proposed in this submission is DxH800 v3.8.0 This system is an update to DxH800 v3.0.0 (see K140911) to add a new feature.
Neither the system architecture nor the top-level software architecture have been modified from DxH800 v3.0 to add the Early Sepsis Indicator feature.
The DxH 800 v.3.8.0 user interface and labeling will be offered in English in the U.S. and in French, German, Italian, Spanish, Japanese, Chinese and English outside the U.S.
Additionally, the UniCel DxH 800 Coulter Cellular Analysis System with Early Sepsis Indicator Application uses the currently cleared controls and calibrator provided in Table 1 below.
Mentions image processing
Not Found
Mentions AI, DNN, or ML
Not Found
Input Imaging Modality
Not Found
Anatomical Site
Not Found
Indicated Patient Age Range
Adult patients
Intended User / Care Setting
Emergency department, clinical laboratories
Description of the training set, sample size, data source, and annotation protocol
Not Found
Description of the test set, sample size, data source, and annotation protocol
Not Found
Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)
Effect of Incomplete Lysing on MDW:
- Testing Approach: To evaluate the effect of incomplete lysing on the MDW parameter results.
- Testing Results: The addition of the incomplete lysis flagging condition causes less than 1.2% of the clinical specimens to have the MDW inhibited. At this rate of flagging the clinical utility of the MDW is not diminished.
Specimen Stability:
- Testing Approach: To characterize the specimen age profile for the MDW parameter on the DxH 800 system using venous whole blood stored at room temperature.
- Testing Results: MDW trends as sample ages. The trend exhibits a quadratic pattern and tends to plateau after 4 hours. Consistent with published literature on monocyte morphological changes, this study shows MDW values tend to increase over the first 3 hours from the draw time and then plateau from 4 to 8 hours post draw at room temperature.
Comparability - Specimen Tube Diameter:
- Testing Approach: To evaluate the effect of mixing using the smaller diameter 8 mm and 11 mm tubes as compared to the standard 13 mm tube on the MDW parameter results.
- Testing Results: The MDW reported from 8 mm and 11 mm diameter tubes is equivalent to the MDW reported from the 13 mm diameter tube.
Comparibility - Sampling modes:
- Testing Approach: To assess the impact on MDW parameter results due to sampling via the Closed Vial Cassette sampling mode and the Open Vial Single-Tube sampling mode on the DxH 800.
- Testing Results: Testing of the MDW parameter in the Open Vial Single-Tube sampling mode was found to be equivalent to the Closed Vial Cassette sampling mode.
Interfering Substances:
- Testing Approach: To assess the effect of interfering substances (lipemia, bilirubin and hemoglobin) on the measurement of the MDW parameter on the DxH 800 system.
- Testing Results:
- Lipids (Triglycerides) at a maximum concentration of 1500 mg/dL do not interfere with MDW measurement.
- Conjugated bilirubin at the maximum concentration of 40 mg/dL does not interfere with the MDW parameter.
- Unconjugated bilirubin at the maximum concentration of 20 mg/dL does not interfere with the MDW parameter.
- Free HGB at a maximum concentration of 1.87 g/dL does not interfere with MDW measurement.
- Hemolysis at a maximum of 2.02 g/dL does not interfere with MDW measurement.
System Precision - Repeatability and Reproducibility:
- Testing Approach: To assess the system precision of the MDW parameter using COULTER 6C Plus Cell Controls on the DxH 800 system.
- Testing Results: Repeatability and Reproducibility study met precision specification. of
§ 866.3215 Device to detect and measure non-microbial analyte(s) in human clinical specimens to aid in assessment of patients with suspected sepsis.
(a)
Identification. A device to detect and measure non-microbial analyte(s) in human clinical specimens to aid in assessment of patients with suspected sepsis is identified as an in vitro device intended for the detection and qualitative and/or quantitative measurement of one or more non-microbial analytes in human clinical specimens to aid in the assessment of patients with suspected sepsis when used in conjunction with clinical signs and symptoms and 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 device's detailed Indications for Use statement describing what the device detects and measures, the results provided to the user, whether the measure is qualitative and/or quantitative, the clinical indications for which the test is to be used, and the specific population(s) for which the device use is intended.
(2) Premarket notification submissions must include detailed documentation of the device description, including (as applicable), all device components, software, ancillary reagents required but not provided, explanation of the device principle and methodology, and for molecular devices include detailed documentation of the primer/probe sequence, design, and rationale for sequence selection.
(3) Premarket notification submissions must include detailed documentation of applicable analytical studies, such as, analytical sensitivity (Limit of Detection, Limit of Blank, and Limit of Quantitation), precision, reproducibility, analytical measuring range, interference, cross-reactivity, and specimen stability.
(4) Premarket notification submissions must include detailed documentation of a prospective clinical study or, if appropriate, results from an equivalent sample set. This detailed documentation must include the following information:
(i) Results must demonstrate adequate device performance relative to a well-accepted comparator.
(ii) Clinical sample results must demonstrate consistency of device output throughout the device measuring range likely to be encountered in the Intended Use population.
(iii) Clinical study documentation must include the original study protocol (including predefined statistical analysis plan), study report documenting support for the Indications for Use(s), and results of all statistical analyses.
(5) Premarket notification submissions must include evaluation of the level of the non-microbial analyte in asymptomatic patients with demographic characteristics (
e.g., age, racial, ethnic, and gender distribution) similar to the Intended Use population.(6) As part of the risk management activities performed under 21 CFR 820.30 design controls, you must document an appropriate end user device training program that will be offered as part of your efforts to mitigate the risk of failure to correctly operate the instrument.
(7) A detailed explanation of the interpretation of results and acceptance criteria must be included in the device's 21 CFR 809.10(b)(9) compliant labeling, and a detailed explanation of the interpretation of the limitations of the samples (
e.g., collected on day of diagnosis) must be included in the device's 21 CFR 809.10(b)(10) compliant labeling.
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March 18, 2019
Beckman Coulter Radha Goolabsingh Director, Regulatory Affairs 11800 SW 147th Ave Miami, Florida 33196-2500
Re: K181599
Trade/Device Name: Unicel DxH 800 Cellular Analysis System with Early Sepsis Indicator Application Regulation Number: 21 CFR 866.3215 Regulation Name: Device to detect and measure non-microbial analyte(s) in human clinical specimens to aid in assessment of patients with suspected sepsis. Regulatory Class: Class II Product Code: QFS, GKZ Dated: June 15, 2018 Received: June 18, 2018
Dear Radha Goolabsingh:
We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food, Drug, and Cosmetic Act (Act) that do not require approval of a premarket approval application (PMA). You mav, therefore, market the device, subject to the general controls provisions of the Act. Although this letter refers to your product as a device, please be avare that some cleared products may instead be combination products. The 510(k) Premarket Notification Database located at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/pmn.cfm identifies combination product submissions. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.
If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. In addition, FDA may publish further announcements concerning your device in the Federal Register.
Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's
1
requirements, including, but not limited to: registration and listing (21 CFR Part 807): labeling (21 CFR Part 801 and Part 809); medical device reporting of medical device-related adverse events) (21 CFR 803) for devices or postmarketing safety reporting (21 CFR 4, Subpart B) for combination products (see https://www.fda.gov/CombinationProducts/GuidanceRegulatoryInformation/ucm597488.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.
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.
Steven R. Gitterman -S for
Uwe Scherf, Ph.D. Director Division of Microbiology Devices Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health
Enclosure
2
Indications for Use
510(k) Number (if known) K181599
Device Name
UniCel DxH 800 Coulter Cellular Analysis System with Early Sepsis Indicator Application
Indications for Use (Describe)
The Unicel DxH 800 Coulter Cellular Analysis System with Early Sepsis Indicator Application is the quantitative measurement of Monocyte Distribution Width (MDW). The Early Sepsis Indicator is intended for use with adult patients presenting to the emergency department, on whom a white cell differential test has been ordered.
MDW is measured from a (K2EDTA) whole-blood venous sample within 2 hours of collection. MDW values greater than 20.0 together with other laboratory findings and clinical information, aids in identifying patients with sepsis or at increased risk of developing sepsis within the first 12 hours of hospital admission.
MDW values greater than 20.0 should be interpreted in association with other clinical information and diagnostic testing. as a proportion of patients without sepsis may have an elevated MDW value at baseline.
MDW values less than or equal to 20.0 cannot rule out sepsis or the development of sepsis within 12 hours of hospital admission. The Early Sepsis Indicator should not be used as the sole basis to determine the absence of sepsis.
The predictive value of the Early Sepsis Indicator for identifying sepsis in patients with hematological abnormalities has not been established.
| 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 800 - Early Sepsis Indicator
Section 5.0: – 510(k) Summary
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510(k) Summary for Unicel DxH 800 Coulter Cellular Analysis System with Early Sepsis Indicator Application
510(k) Owner / Submitter Information
Name: Beckman Coulter Inc. Address: 11800 SW 147th Ave., Miami, FL 33196 Cellular: 786-423-4575 Desk Phone #: (305) 380-2584 Fax: (786) 639-2584 Contact Person: Radha Goolabsingh Email Address: rgoolabsingh(@beckman.com
Date Submitted: June 15, 2018
Device Name and Classification
Trade Name: Unicel DxH 800 Coulter Cellular Analysis System with Early Sepsis Indicator Application
Common Name: Early Sepsis Indicator
Classification: Class II (Special Controls)
Classification Name: Device to detect and measure non-microbial analyte(s) in human clinical specimens to aid in assessment of patients with suspected sepsis (21 CFR 866.3215)
Product Code: QFS
Panel: 83- Division of Microbiology Devices
Unicel DxH 800 Cellular Analysis System - Last 510(k) Clearance: K140911, 09/05/2014
Predicate Device Information
| Predicate Product | 510(k)
Number | Date
Cleared | Classification | 21 CFR | Product
Code |
|---------------------------|------------------|-----------------|-----------------------------------|----------|-----------------|
| VIDAS BRAHMS
PCT (PCT) | K162827 | 02/23/2017 | Class II
(Special
Controls) | 866.3215 | PMT |
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Image /page/5/Picture/1 description: The image shows the logo for Beckman Coulter. The logo consists of a red circle with two white curved lines inside, followed by the words "BECKMAN" and "COULTER" in bold, black letters. The words are stacked on top of each other, with "BECKMAN" on the top line and "COULTER" on the bottom line.
Device Description
Systems Overview
The Early Sepsis Indicator (ESI) requires the use of the UniCel DxH 800 Coulter Cellular Analysis System (DxH 800) and its reagents, controls and calibrators last cleared under 510(k) K140911.
The UniCel DxH 800 Coulter Cellular Analysis System contains a quantitative, automated hematology analyzer (DxH 800) designed for in vitro diagnostic use in screening patient populations by clinical laboratories. The system provides a Complete Blood Count (CBC), Leukocyte 5 Part Differential (Diff), Reticulocyte (Retic), Nucleated Red Blood Cell (NRBC) on whole blood, as well as, Total Nucleated Count (TNC), and Red Cell Count (RBC) on Body Fluids (cerebrospinal, serous and synovial). This submission adds a new parameter, Monocyte Distribution Width (MDW) to those mentioned above. This parameter has been shown to aid in the early detection of Sepsis in emergency room patients.
The system consists of two primary components, the workstation and the DxH 800 analyzer as shown in Figure 1. DxH 800 System Configuration. The primary function of the DxH 800 analyzer is to process samples and provide results to the workstation. The primary functions of the workstation are: user interface, system control, results processing and storage and external communications. The analyzer runs embedded code and the workstation runs Microsoft Windows 7 Operating System (OS).
Optionally, the workstation can be connected to:
- A printer for creating reports: ●
- A Laboratory Information System (LIS) for receiving test orders and releasing . results; and
- Pro-Service Remote Management System (RMS) which provides secure access to . the DxH800 workstation for BCI Service Personnel to perform troubleshooting, system monitoring and for assisting customers.
The version of the system proposed in this submission is DxH800 v3.8.0 This system is an update to DxH800 v3.0.0 (see K140911) to add a new feature.
Neither the system architecture nor the top-level software architecture have been modified from DxH800 v3.0 to add the Early Sepsis Indicator feature.
The DxH 800 v.3.8.0 user interface and labeling will be offered in English in the U.S. and in French, German, Italian, Spanish, Japanese, Chinese and English outside the U.S.
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Image /page/6/Picture/0 description: The image shows the logo for Beckman Coulter. The logo consists of a red oval shape on the left side, with two curved white lines running through it. To the right of the oval shape is the text "BECKMAN" in a bold, sans-serif font, stacked above the text "COULTER" in the same font.
Image /page/6/Figure/2 description: The image shows a network diagram of a laboratory information system (LIS). The LIS server is connected to a workstation via an RS-232 cable. The workstation is also connected to a printer via USB, a switch via Ethernet, and the RMS via Ethernet to the Internet. The switch is connected to a DxH 800 analyzer via Ethernet.
Figure 1. DxH 800 System Configuration
Additionally, the UniCel DxH 800 Coulter Cellular Analysis System with Early Sepsis Indicator Application uses the currently cleared controls and calibrator provided in Table 1 below.
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Image /page/7/Picture/0 description: The image shows the logo for Beckman Coulter. The logo consists of a red circle with two white curved lines inside, followed by the words "BECKMAN" in bold black letters on the top line and "COULTER" in bold black letters on the bottom line. The logo is simple and modern, and the colors are eye-catching.
Table 1: Summary of Device Components, Product Description, Proposed Classification and Proposed Predicate:
| Product | 510(k) Clearance Status | Description | Classification | Proposed Predicate |
|---|---|---|---|---|
| DxH 800 | ||||
| Hematology | ||||
| Analyzer | Existing Product | |||
| (cleared under K140911) |
Modified- Addition of new
parameter (MDW)
requiring Software
algorithm modifications | The UniCel DxH 800 COULTER Cellular Analysis
System (DxH 800) is intended for In Vitro Diagnostic
Use in clinical laboratories. The DxH 800 System
provides automated complete blood count, leukocyte
differential, nucleated red blood cell (NRBC)
enumeration and reticulocyte analysis as well as an
automated method for enumeration of the Total
Nucleated Cells (TNC) and Red Blood Cells (RBC) in
body fluids. | Class II, GKZ,
864.5220, Hematology,
Automated Differential
Cell Counter
Early Sepsis Indicator
Application: 866.3215,
Product code (QFS) | VIDAS
B.R.A.H.M.S. PCT
(PCT) (K16287)
(Paper Predicate) |
| COULTER DxH
Diff Pack | Existing Product
(Included in K140911)
No change | The COULTER DxH Diff Pack is an erythrolytic reagent
and a leukocyte preservative used to perform a five-
part differential analysis using VCSn technology on
the DxH 800/DxH 600. | Class I Exempt, GGK,
864.8540, Hematology,
Red cell lysing reagent | N/A |
| COULTER DxH
Diluent | Existing Product
(Included in K140911)
No change | COULTER DXH Diluent provides the ability to analyze
portions of the diluted blood samples for different
blood cell types and measure hemoglobin on the DxH
800/600. Acts as a rinsing agent on all DxH Systems. | Class I Exempt, GIF,
864.8200, Hematology,
Blood cell diluent | N/A |
| COULTER DxH
Cleaner | Existing Product
(Included in K140911)
No change | DxH Cleaner is a cleaning agent for use on the DxH
System components that come in contact with blood
samples. | Class I Exempt, JCB,
864.4010, Hematology,
General Purpose
Reagent | N/A |
| COULTER 6C
Plus Cell Control | Existing Product
(6C Cell Control)
(cleared under K081822) | COULTER 6C Plus Cell Control is an integrated
control that enables monitoring of system
performance for CBC, Diff, NRBC, MDW and LDW
parameters. The COULTER 6C Plus Cell Control | Class II, Exempt, JPK,
864.8625, Hematology,
Quality Control
Mixture | COULTER 6C Cell
Control
(K081822) |
| Product | 510(k) Clearance Status | Description | Classification | Proposed Predicate |
| COULTER Latron
CP-X Control | Modified - to provide two
new parameters (LDW and
MDW) for control
monitoring of the
calculation of cellular
dispersion
Existing Product
(cleared under K885028)
Modified - with tighter
expected ranges for control
monitoring of the
differential volume
measurement | proposed for use with the Sepsis Application is the
current COULTER 6C Cell Control (K081822),
assayed to include values for the MDW and LDW
parameters. LDW is not intended for the reporting of
patient results.
COULTER LATRON CP-X is a suspension of stable
polystyrene particles of uniform size with a diameter
CV of ≤3.0%. Latron CP-X is used by customers as
part of the daily quality control procedure to monitor
the stability of the electrical processing and the fluidic
flow rate systems used to measure the volume (size),
conductivity and light scattering characteristics of
cells as they pass through the flow cell. It is also used
by Beckman Coulter manufacturing and service
engineers to calibrate the differential volume
measurements | Class II, GKL,
864.5220, Hematology,
Automated Differential
Cell Counter | COULTER Latron
CP-X Control
(K885028) |
| *Coulter S-CAL
Calibrator | Existing Product
(cleared under K840794)
No change | The current COULTER S-CAL Calibrator used with
the DxH 800 is intended for customers to determine
the calibration factors for directly measured CBC
parameters: it is not required differential parameters | Class II, Exempt, KRY,
864.8175, Calibrator
for Platelet Counting | N/A |
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*Note: The current COULTER S-CAL Calibrator used with the DxH 800 is intended for customers to determine the calibration factors for directly measured CBC parameters; it is not required for differential parameters. Since the MDW and LDW parameters are derived from the monocyte and lymphocyte differential, the use of a calibrator by the customer is not required for the Sepsis Application.
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Intended Use:
UniCel DxH 800 Coulter Cellular Analysis System with Early Sepsis Indicator Application:
The Unicel DxH 800 Coulter Cellular Analysis System with Early Sepsis Indicator Application is the quantitative measurement of Monocyte Distribution Width (MDW). The Early Sepsis Indicator is intended for use with adult patients presenting to the emergency department, on whom a white cell differential test has been ordered.
MDW is measured from a (K2EDTA) whole-blood venous sample within 2 hours of collection. MDW values greater than 20.0 together with other laboratory findings and clinical information, aids in identifying patients with sepsis or at increased risk of developing sepsis within the first 12 hours of hospital admission.
MDW values greater than 20.0 should be interpreted in association with other clinical information and diagnostic testing, as a proportion of patients without sepsis may have an elevated MDW value at baseline.
MDW values less than or equal to 20.0 cannot rule out sepsis or the development of sepsis within 12 hours of hospital admission. The Early Sepsis Indicator should not be used as the sole basis to determine the absence of sepsis.
The predictive value of the Early Sepsis Indicator for identifying sepsis in patients with hematological abnormalities has not been established.
Indication for Use:
See Intended Use above.
Overall Comparison between Early Sepsis Indicator and the Predicate:
Table 2 provides an overall comparison of the differences and similarities against the Predicate Device (VIDAS BRAHMS PCT (PCT) K162827).
| Item | DxH 800 Coulter Cellular Analysis
System with Early Sepsis Indicator
Application | Predicate Device (Paper Predicate)
VIDAS BRAHMS PCT (PCT) K162827 |
|-----------------------------------------|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Intended Use and
Indications for Use | The Unicel DxH 800 Coulter
Cellular Analysis System with Early
Sepsis Indicator Application is the
quantitative measurement of
Monocyte Distribution Width | VIDAS B·R·A·H·M·S PCT (PCT) is an
automated test for use on the instruments of
the VIDAS family for the determination of
human procalcitonin in human serum or
plasma (lithium heparinate) using the ELFA
(Enzyme-Linked Fluorescent Assay)
technique. |
| Item | DxH 800 Coulter Cellular Analysis
System with Early Sepsis Indicator
Application | Predicate Device (Paper Predicate)
VIDAS BRAHMS PCT (PCT) K162827 |
| | (MDW). The Early Sepsis Indicator
is intended for use with adult
patients presenting to the emergency
department, on whom a white cell
differential test has been ordered. | Used in conjunction with other laboratory
findings and clinical assessments, VIDAS
BRAHMS PCT is intended for use as follows:
• to aid in the risk assessment of critically ill
patients on their first day of ICU admission
for progression to severe sepsis and septic
shock, |
| | MDW is measured from a
(K2EDTA) whole-blood venous
sample within 2 hours of collection.
MDW values greater than 20.0
together with other laboratory
findings and clinical information,
aids in identifying patients with
sepsis or at increased risk of
developing sepsis within the first 12
hours of hospital admission.
MDW values greater than 20.0
should be interpreted in association
with other clinical information and
diagnostic testing, as a proportion of
patients without sepsis may have an
elevated MDW value at baseline. | • to aid in assessing the cumulative 28-day
risk of all-cause mortality for patients
diagnosed with severe sepsis or septic shock
in the ICU or when obtained in the emergency
department or other medical wards prior to
ICU admission, using a change in PCT level
over time
•to aid in decision making on antibiotic
therapy for patients with suspected or
confirmed lower respiratory tract infections
(LRTI) defined as community-acquired
pneumonia (CAP), acute bronchitis, and acute
exacerbation of chronic obstructive
pulmonary disease (AECOPD) – in an
inpatient setting or an emergency department,
• to aid in decision making on antibiotic
discontinuation for patients with suspected or
confirmed sepsis. |
| | MDW values less than or equal to
20.0 cannot rule out sepsis or the
development of sepsis within 12
hours of hospital admission. The
Early Sepsis Indicator should not be
used as the sole basis to determine
the absence of sepsis.
The predictive value of the Early
Sepsis Indicator for identifying
sepsis in patients with hematological | |
| Item | DxH 800 Coulter Cellular Analysis
System with Early Sepsis Indicator
Application | Predicate Device (Paper Predicate)
VIDAS BRAHMS PCT (PCT) K162827 |
| | abnormalities has not been
established. | |
| Specimen | Venous Whole Blood | Human Serum or Plasma (lithium heparinate) |
| Analyte | MDW Parameter | Procalcitonin (PCT) |
| Automated | Automated Hematology Analyzer | Automated Assay |
| Assay Technique | Whole blood analysis and cellular
differentiation on the DxH800 | ELFA (Enzyme-Linked Fluorescent Assay)
technique |
| Assay Principle | Coulter Principle:
Volume, Conductivity, Light Scatter
Analysis (VCSn) Technology using :
Aperture impedance (DC)
Conductivity (RF)
Laser Light Scatter (Multiple angles)
Laser Light Absorbance | Immunoassay based on sandwich principle |
| Detection method | VCSn | Fluorescence (ELFA) of 4-methy-
umbelliferyl measured at 450 nm |
| Assay/Parameter
Duration | ≥90 specimens per hour (40 sec/cycle)
for CBC and Diff with NRBC cycle
(approximately 40 seconds per sample) | Approximately 20 minutes |
| Combination Devices | N/A | Instruments of the VIDAS family: VIDAS,
miniVIDAS or VIDAS 3 |
| Antibodies | N/A | Conjugate: Alkaline
phosphatase-labeled mouse
monoclonal anti-human
procalcitonin
Solid phase: Mouse
monoclonal anti-procalcitonin
immunoglobulins coated on interior of the
SPRSample |
| Sample Volume | Automatic, cap-piercing 165 uL | 200 µL |
Table 2. Overall Comparison hetween ESI and the Predicate
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11
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| Study | Testing Approach | FDA Guidance
Documents | Standards/ References | Testing Results |
|---------------------------------------------|----------------------------------------------------------------------------------------------------------------------------------------------------------------|-----------------------------|--------------------------------------------------------------------------------------------------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| | | Performance - Bench Testing | | |
| Effect of
Incomplete
Lysing on
MDW | To evaluate the effect
of incomplete lysing
on the MDW
parameter results | None | None | The addition of the incomplete
lysis flagging condition causes
less than 1.2% of the clinical
specimens to have the MDW
inhibited. At this rate of flagging
the clinical utility of the MDW is
not diminished. |
| Specimen
Stability | To characterize the
specimen age profile
for the MDW
parameter on the
DxH 800 system
using venous whole
blood stored at room
temperature. | None | CLSI EP25-A: Evaluation of
Stability of In Vitro Diagnostic
Reagents; Approved Guideline –
September 2009 | MDW trends as sample ages. The
trend exhibits a quadratic pattern
and tends to plateau after 4 hours.
Consistent with published
literature on monocyte
morphological changes, this study
shows MDW values tend to
increase over the first 3 hours
from the draw time and then
plateau from 4 to 8 hours post
draw at room temperature |
Table 3: Summary of the MDW Parameter Performance Testing
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| Study | Testing Approach | FDA Guidance Documents | Standards/ References | Testing Results |
|---|---|---|---|---|
| Comparability |
- Specimen
Tube Diameter | To evaluate the effect
of mixing using the
smaller diameter 8
mm and 11 mm tubes
as compared to the
standard 13 mm tube
on the MDW
parameter results. | None | CLSI H26-A2: Validation
and Quality Assurance
of Automated
Hematology Analyzers;
Approved Standard – Second
Edition - June 2010
EP09-A3: Measurement
Procedure Comparison and Bias
Estimation Using Patient
Samples; Approved Guideline –
Third Edition – August 2013 | The MDW reported from 8 mm
and 11 mm diameter tubes is
equivalent to the MDW reported
from the 13 mm diameter tube. |
| Comparibility
- Sampling
modes | To assess the impact
on MDW parameter
results due to
sampling via the
Closed Vial Cassette
sampling mode and
the Open Vial
Single-Tube
sampling mode on
the DxH 800. | None | CLSI H26-A2: Validation,
Verification and Quality
Assurance of Automated
Hematology Analyzers;
Approved Standard – Second
Edition - June 2010
CLSI EP09-A3: Measurement
Procedure Comparison and Bias
Estimation Using Patient
Samples; Approved Guideline -
Third Edition - August 2013 | Testing of the MDW parameter in
the Open Vial Single-Tube
sampling mode was found to be
equivalent to the Closed Vial
Cassette sampling mode. |
| Interfering
Substances | To assess the effect
of interfering
substances (lipemia,
bilirubin and
hemoglobin) on the
measurement of the
MDW parameter on
the DxH 800 system. | None | CLSI H26-A2: Validation, Verification and Quality Assurance of Automated Hematology Analyzers - June 2010 | Lipids (Triglycerides) at a maximum concentration of 1500 mg/dL do not interfere with MDW measurement. |
| | | | CLSI C56-A: Hemolysis, Icterus, and Lipemia/Turbidity Indices as Indicators of Interference in Clinical Laboratory Analysis; Approved Guideline - July 2012 | Conjugated bilirubin at the maximum concentration of 40 mg/dL does not interfere with the MDW parameter.
Unconjugated bilirubin at the maximum concentration of 20 mg/dL does not interfere with the MDW parameter. |
| | | | CLSI EP07-A2: Interference testing in Clinical Chemistry; Approved Guideline - Second Edition - November 2005 | Free HGB at a maximum concentration of 1.87 g/dL does not interfere with MDW measurement.
Hemolysis at a maximum of 2.02 g/dL does not interfere with MDW measurement. |
| Study | Testing Approach | FDA Guidance
Documents | Standards/ References | Testing Results |
| Performance - Clinical Testing | | | | |
| System
Precision -
Repeatability
and
Reproducibility | To assess the system
precision of the
MDW parameter
using COULTER 6C
Plus Cell Controls on
the DxH 800 system. | 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
December 4, 2001 –
Section 13:
Specimens. | CLSI EP05-A3 Evaluation of
precision of Quantitative
Measurement Procedures ;
Approved Guideline – Third
Edition | Repeatability and Reproducibility
study met precision specification.
of $\le$ 10% CV and $\le$ 15% CV,
respectively by site and all sites
combined. |
| System
Precision-
Repeatability
Profile | To demonstrate the
system precision
performance of
MDW on the DxH
800 | 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
December 4, 2001 –
Section 13:
Specimens. | CLSI H26-A2 Validation,
Verification, and Quality
Assurance of Automated
Hematology Analyzers,
Approved Standard – 2nd
Edition; June 2010
CLSI EP05-A3 Evaluation of
precision of Quantitative
Measurement Procedures ;
Approved Guideline – Third
Edition | System repeatability performance
acceptance criteria were $\le$ 10%
for all parameters. |
| Study | Testing Approach | FDA Guidance Documents | Standards/ References | Testing Results |
| Adult
Reference
Interval | To assess the normal
reference interval of
MDW for apparently
healthy adult males
and females. A total
of 146 specimens
were collected
consisting of 70
females and 76 males
to establish the
normal reference
interval of MDW. | None | CLSI EP28-A3c, Defining,
Establishing, and Verifying
Reference Intervals in the
Clinical Laboratory; Approved
Guideline, (10/2010) | The adult normal reference
interval assessed for MDW on the
DxH 800 system across all sites
was found to be between the
lower limit of 13.98 and the upper
limit of 21.28. Data was included
in the product labeling, however
the upper limit of normal will not
be used for MDW decision-
making. |
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| Study | Testing Approach | FDA Guidance
Documents | Standards/ References | Testing Results |
|----------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Clinical
Accuracy | To assess the
diagnostic ability of
MDW. A multi-
center prospective
cohort study was
conducted to
clinically validate the
performance of
Monocyte Volume
Distribution Width
(MDW) parameter on
the DxH 800
hematology analyzer,
as an aid in the early
detection of sepsis in
adult patients
presenting to the
emergency
department (ED). | 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
December 4, 2001
Statistical Guidance
on Reporting Results
from Studies
Evaluating Diagnostic
Tests; Final Guidance
for Industry and FDA
Staff; March 2007 | CLSI EP12-A2: User Protocol
for Evaluation of Qualitative
Test Performance; Approve
Guideline. Second Edition
guideline.
CLSI EP24-A2: Assessment of
the Diagnostic Accuracy of
Laboratory Tests Using
Receiver Operating
Characteristic Curves;
Approved Guideline – Second
Edition. 2011. | The study results support the
proposed intended use and
indications for use. The study
validated the two (2) predefined
cut-offs and demonstrated that the
lower limit of sensitivity and
specificity were within
acceptance criteria for both cut-
offs. However, the study
demonstrated that an MDW cut-
off of 20.0 units provided an
optimum diagnostic ability by
balancing the ability to detect
positive patients (sensitivity) and
negative patients (specificity) and
this is the cut-off selected. |
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Substantial Equivalence Conclusion:
The conclusions drawn from the testing discussed in Section 20, which demonstrate clinical accuracy (sensitivity and specificity) of the MDW parameter and together with multiple literature citations (as provided in this submission), supports the use of MDW as an aid in the early detection of adult patients with or developing sepsis.
Furthermore, it can be concluded that the submitted information in this premarket notification is complete, offers a reasonable assurance of safety and effectiveness and supports a substantial equivalence determination for the DxH 800 Coulter Cellular Analysis System with Early Sepsis Indicator Application.