(273 days)
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.
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).
Here's the breakdown of the acceptance criteria and study detailed in the provided document:
Acceptance Criteria and Device Performance for UniCel DxH 800 Cellular Analysis System with Early Sepsis Indicator Application
The device is intended for the quantitative measurement of Monocyte Distribution Width (MDW) to aid in identifying adult patients with sepsis or at increased risk of developing sepsis within the first 12 hours of hospital admission. The key acceptance criterion for clinical accuracy revolves around sensitivity and specificity at a specified MDW cut-off.
1. Table of Acceptance Criteria and Reported Device Performance
| Acceptance Criteria Study | Acceptance Criteria (Threshold) | Reported Device Performance (Result) |
|---|---|---|
| Clinical Accuracy (MDW Cut-off of 20.0) | - Sensitivity within predefined lower limit | - Validated the predefined cut-offs |
| - Specificity within predefined lower limit | - Demonstrated that the lower limit of sensitivity and specificity were within acceptance criteria for both cut-offs. |
Note: The document states that 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 thus this cut-off was selected. Detailed numerical values for sensitivity and specificity at this cut-off are not explicitly provided in the table, but the text assures they met the acceptance criteria.
2. Sample Size and Data Provenance for Test Set
- Sample Size: Not explicitly stated for the "test set" in a distinct way, but the "Clinical Accuracy" study states it was a "multi-center prospective cohort study."
- Data Provenance:
- Country of Origin: Not specified in the provided text.
- Retrospective or Prospective: Primarily prospective. The clinical accuracy study was a "multi-center prospective cohort study."
3. Number of Experts and Qualifications for Ground Truth
- Number of Experts: Not specified.
- Qualifications of Experts: Not specified.
Note: The document mentions "clinical information and diagnostic testing" and "other laboratory findings" were used in conjunction with MDW values, implying expert judgment in establishing the ground truth for sepsis diagnosis.
4. Adjudication Method
- Adjudication Method: Not specified.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
- MRMC Study: No, an MRMC comparative effectiveness study was not done. This device measures a quantitative biomarker (MDW) from a blood sample, not something interpreted by human readers from images or complex data.
6. Standalone (Algorithm Only) Performance
- Standalone Performance: Yes, the fundamental performance assessed is the standalone diagnostic ability of the MDW parameter as an aid in identifying sepsis. The clinical accuracy study directly evaluated the MDW parameter's performance in detecting sepsis.
7. Type of Ground Truth Used
- Type of Ground Truth: The ground truth for sepsis diagnosis was established based on "other laboratory findings and clinical information" and "diagnostic testing." This suggests a comprehensive clinical diagnosis of sepsis, likely involving a combination of clinical assessment, laboratory parameters (beyond MDW), and potentially culture results or other confirmatory tests, as determined by clinicians.
8. Sample Size for Training Set
- Sample Size for Training Set: Not explicitly stated as a separate "training set" in the context of machine learning model development. The document focuses on the validation of the MDW parameter and its cut-off.
Note: The MDW parameter itself is a quantitative measurement derived from hematology analyzer data, not a machine learning model that would typically have a distinct training set in the conventional sense. The "training" or development of the algorithm to calculate MDW would have occurred prior to this validation study, but details are not provided here.
9. How Ground Truth for Training Set Was Established
- How Ground Truth for Training Set Was Established: Not specified, as a distinct training set for a machine learning model is not explicitly mentioned or implied for the MDW parameter's development in this document. The MDW value is a quantitative measurement from the analyzer, not a diagnosis itself.
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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
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requirements, including, but not limited to: registration and listing (21 CFR Part 807): labeling (21 CFR Part 801 and Part 809); medical device reporting of medical device-related adverse events) (21 CFR 803) for devices or postmarketing safety reporting (21 CFR 4, Subpart B) for combination products (see https://www.fda.gov/CombinationProducts/GuidanceRegulatoryInformation/ucm597488.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
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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 | DateCleared | Classification | 21 CFR | ProductCode |
|---|---|---|---|---|---|
| VIDAS BRAHMSPCT (PCT) | K162827 | 02/23/2017 | Class II(SpecialControls) | 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 800HematologyAnalyzer | Existing Product(cleared under K140911)Modified- Addition of newparameter (MDW)requiring Softwarealgorithm modifications | The UniCel DxH 800 COULTER Cellular AnalysisSystem (DxH 800) is intended for In Vitro DiagnosticUse in clinical laboratories. The DxH 800 Systemprovides automated complete blood count, leukocytedifferential, nucleated red blood cell (NRBC)enumeration and reticulocyte analysis as well as anautomated method for enumeration of the TotalNucleated Cells (TNC) and Red Blood Cells (RBC) inbody fluids. | Class II, GKZ,864.5220, Hematology,Automated DifferentialCell CounterEarly Sepsis IndicatorApplication: 866.3215,Product code (QFS) | VIDASB.R.A.H.M.S. PCT(PCT) (K16287)(Paper Predicate) |
| COULTER DxHDiff Pack | Existing Product(Included in K140911)No change | The COULTER DxH Diff Pack is an erythrolytic reagentand a leukocyte preservative used to perform a five-part differential analysis using VCSn technology onthe DxH 800/DxH 600. | Class I Exempt, GGK,864.8540, Hematology,Red cell lysing reagent | N/A |
| COULTER DxHDiluent | Existing Product(Included in K140911)No change | COULTER DXH Diluent provides the ability to analyzeportions of the diluted blood samples for differentblood cell types and measure hemoglobin on the DxH800/600. Acts as a rinsing agent on all DxH Systems. | Class I Exempt, GIF,864.8200, Hematology,Blood cell diluent | N/A |
| COULTER DxHCleaner | Existing Product(Included in K140911)No change | DxH Cleaner is a cleaning agent for use on the DxHSystem components that come in contact with bloodsamples. | Class I Exempt, JCB,864.4010, Hematology,General PurposeReagent | N/A |
| COULTER 6CPlus Cell Control | Existing Product(6C Cell Control)(cleared under K081822) | COULTER 6C Plus Cell Control is an integratedcontrol that enables monitoring of systemperformance for CBC, Diff, NRBC, MDW and LDWparameters. The COULTER 6C Plus Cell Control | Class II, Exempt, JPK,864.8625, Hematology,Quality ControlMixture | COULTER 6C CellControl(K081822) |
| Product | 510(k) Clearance Status | Description | Classification | Proposed Predicate |
| COULTER LatronCP-X Control | Modified - to provide twonew parameters (LDW andMDW) for controlmonitoring of thecalculation of cellulardispersionExisting Product(cleared under K885028)Modified - with tighterexpected ranges for controlmonitoring of thedifferential volumemeasurement | proposed for use with the Sepsis Application is thecurrent COULTER 6C Cell Control (K081822),assayed to include values for the MDW and LDWparameters. LDW is not intended for the reporting ofpatient results.COULTER LATRON CP-X is a suspension of stablepolystyrene particles of uniform size with a diameterCV of ≤3.0%. Latron CP-X is used by customers aspart of the daily quality control procedure to monitorthe stability of the electrical processing and the fluidicflow rate systems used to measure the volume (size),conductivity and light scattering characteristics ofcells as they pass through the flow cell. It is also usedby Beckman Coulter manufacturing and serviceengineers to calibrate the differential volumemeasurements | Class II, GKL,864.5220, Hematology,Automated DifferentialCell Counter | COULTER LatronCP-X Control(K885028) |
| *Coulter S-CALCalibrator | Existing Product(cleared under K840794)No change | The current COULTER S-CAL Calibrator used withthe DxH 800 is intended for customers to determinethe calibration factors for directly measured CBCparameters: it is not required differential parameters | Class II, Exempt, KRY,864.8175, Calibratorfor 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 AnalysisSystem with Early Sepsis IndicatorApplication | Predicate Device (Paper Predicate)VIDAS BRAHMS PCT (PCT) K162827 |
|---|---|---|
| Intended Use andIndications for Use | The Unicel DxH 800 CoulterCellular Analysis System with EarlySepsis Indicator Application is thequantitative measurement ofMonocyte Distribution Width | VIDAS B·R·A·H·M·S PCT (PCT) is anautomated test for use on the instruments ofthe VIDAS family for the determination ofhuman procalcitonin in human serum orplasma (lithium heparinate) using the ELFA(Enzyme-Linked Fluorescent Assay)technique. |
| Item | DxH 800 Coulter Cellular AnalysisSystem with Early Sepsis IndicatorApplication | Predicate Device (Paper Predicate)VIDAS BRAHMS PCT (PCT) K162827 |
| (MDW). The Early Sepsis Indicatoris intended for use with adultpatients presenting to the emergencydepartment, on whom a white celldifferential test has been ordered. | Used in conjunction with other laboratoryfindings and clinical assessments, VIDASBRAHMS PCT is intended for use as follows:• to aid in the risk assessment of critically illpatients on their first day of ICU admissionfor progression to severe sepsis and septicshock, | |
| MDW is measured from a(K2EDTA) whole-blood venoussample within 2 hours of collection.MDW values greater than 20.0together with other laboratoryfindings and clinical information,aids in identifying patients withsepsis or at increased risk ofdeveloping sepsis within the first 12hours of hospital admission.MDW values greater than 20.0should be interpreted in associationwith other clinical information anddiagnostic testing, as a proportion ofpatients without sepsis may have anelevated MDW value at baseline. | • to aid in assessing the cumulative 28-dayrisk of all-cause mortality for patientsdiagnosed with severe sepsis or septic shockin the ICU or when obtained in the emergencydepartment or other medical wards prior toICU admission, using a change in PCT levelover time•to aid in decision making on antibiotictherapy for patients with suspected orconfirmed lower respiratory tract infections(LRTI) defined as community-acquiredpneumonia (CAP), acute bronchitis, and acuteexacerbation of chronic obstructivepulmonary disease (AECOPD) – in aninpatient setting or an emergency department,• to aid in decision making on antibioticdiscontinuation for patients with suspected orconfirmed sepsis. | |
| MDW values less than or equal to20.0 cannot rule out sepsis or thedevelopment of sepsis within 12hours of hospital admission. TheEarly Sepsis Indicator should not beused as the sole basis to determinethe absence of sepsis.The predictive value of the EarlySepsis Indicator for identifyingsepsis in patients with hematological | ||
| Item | DxH 800 Coulter Cellular AnalysisSystem with Early Sepsis IndicatorApplication | Predicate Device (Paper Predicate)VIDAS BRAHMS PCT (PCT) K162827 |
| abnormalities has not beenestablished. | ||
| 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 cellulardifferentiation on the DxH800 | ELFA (Enzyme-Linked Fluorescent Assay)technique |
| Assay Principle | Coulter Principle:Volume, Conductivity, Light ScatterAnalysis (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/ParameterDuration | ≥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: Alkalinephosphatase-labeled mousemonoclonal anti-humanprocalcitoninSolid phase: Mousemonoclonal anti-procalcitoninimmunoglobulins coated on interior of theSPRSample |
| Sample Volume | Automatic, cap-piercing 165 uL | 200 µL |
Table 2. Overall Comparison hetween ESI and the Predicate
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Image /page/10/Picture/1 description: The image shows the Beckman Coulter logo. The logo consists of a red oval shape with two white curved lines inside, resembling a stylized eye or a double helix. To the right of the symbol, the words "BECKMAN" and "COULTER" are stacked on top of each other in a bold, sans-serif font. The overall design is clean and modern, conveying a sense of innovation and precision.
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Image /page/11/Picture/0 description: The image shows the logo for Beckman Coulter. The logo consists of a red circle with two white curved lines inside, and the words "BECKMAN" and "COULTER" in black, stacked on top of each other. The logo is simple and modern, and the colors are eye-catching.
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| Study | Testing Approach | FDA GuidanceDocuments | Standards/ References | Testing Results |
|---|---|---|---|---|
| Performance - Bench Testing | ||||
| Effect ofIncompleteLysing onMDW | To evaluate the effectof incomplete lysingon the MDWparameter results | None | None | The addition of the incompletelysis flagging condition causesless than 1.2% of the clinicalspecimens to have the MDWinhibited. At this rate of flaggingthe clinical utility of the MDW isnot diminished. |
| SpecimenStability | To characterize thespecimen age profilefor the MDWparameter on theDxH 800 systemusing venous wholeblood stored at roomtemperature. | None | CLSI EP25-A: Evaluation ofStability of In Vitro DiagnosticReagents; Approved Guideline –September 2009 | MDW trends as sample ages. Thetrend exhibits a quadratic patternand tends to plateau after 4 hours.Consistent with publishedliterature on monocytemorphological changes, this studyshows MDW values tend toincrease over the first 3 hoursfrom the draw time and thenplateau from 4 to 8 hours postdraw 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- SpecimenTube Diameter | To evaluate the effectof mixing using thesmaller diameter 8mm and 11 mm tubesas compared to thestandard 13 mm tubeon the MDWparameter results. | None | CLSI H26-A2: Validationand Quality Assuranceof AutomatedHematology Analyzers;Approved Standard – SecondEdition - June 2010EP09-A3: MeasurementProcedure Comparison and BiasEstimation Using PatientSamples; Approved Guideline –Third Edition – August 2013 | The MDW reported from 8 mmand 11 mm diameter tubes isequivalent to the MDW reportedfrom the 13 mm diameter tube. |
| Comparibility- Samplingmodes | To assess the impacton MDW parameterresults due tosampling via theClosed Vial Cassettesampling mode andthe Open VialSingle-Tubesampling mode onthe DxH 800. | None | CLSI H26-A2: Validation,Verification and QualityAssurance of AutomatedHematology Analyzers;Approved Standard – SecondEdition - June 2010CLSI EP09-A3: MeasurementProcedure Comparison and BiasEstimation Using PatientSamples; Approved Guideline -Third Edition - August 2013 | Testing of the MDW parameter inthe Open Vial Single-Tubesampling mode was found to beequivalent to the Closed VialCassette sampling mode. |
| InterferingSubstances | To assess the effectof interferingsubstances (lipemia,bilirubin andhemoglobin) on themeasurement of theMDW parameter onthe 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 GuidanceDocuments | Standards/ References | Testing Results |
| Performance - Clinical Testing | ||||
| SystemPrecision -RepeatabilityandReproducibility | To assess the systemprecision of theMDW parameterusing COULTER 6CPlus Cell Controls onthe DxH 800 system. | Class II SpecialControls GuidanceDocument: PremarketNotifications forAutomatedDifferential CellCounters for Immatureor Abnormal BloodCells; Final Guidancefor Industry and FDADecember 4, 2001 –Section 13:Specimens. | CLSI EP05-A3 Evaluation ofprecision of QuantitativeMeasurement Procedures ;Approved Guideline – ThirdEdition | Repeatability and Reproducibilitystudy met precision specification.of $\le$ 10% CV and $\le$ 15% CV,respectively by site and all sitescombined. |
| SystemPrecision-RepeatabilityProfile | To demonstrate thesystem precisionperformance ofMDW on the DxH800 | Class II SpecialControls GuidanceDocument: PremarketNotifications forAutomatedDifferential CellCounters for Immatureor Abnormal BloodCells; Final Guidancefor Industry and FDADecember 4, 2001 –Section 13:Specimens. | CLSI H26-A2 Validation,Verification, and QualityAssurance of AutomatedHematology Analyzers,Approved Standard – 2ndEdition; June 2010CLSI EP05-A3 Evaluation ofprecision of QuantitativeMeasurement Procedures ;Approved Guideline – ThirdEdition | System repeatability performanceacceptance criteria were $\le$ 10%for all parameters. |
| Study | Testing Approach | FDA Guidance Documents | Standards/ References | Testing Results |
| AdultReferenceInterval | To assess the normalreference interval ofMDW for apparentlyhealthy adult malesand females. A totalof 146 specimenswere collectedconsisting of 70females and 76 malesto establish thenormal referenceinterval of MDW. | None | CLSI EP28-A3c, Defining,Establishing, and VerifyingReference Intervals in theClinical Laboratory; ApprovedGuideline, (10/2010) | The adult normal referenceinterval assessed for MDW on theDxH 800 system across all siteswas found to be between thelower limit of 13.98 and the upperlimit of 21.28. Data was includedin the product labeling, howeverthe upper limit of normal will notbe used for MDW decision-making. |
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| Study | Testing Approach | FDA GuidanceDocuments | Standards/ References | Testing Results |
|---|---|---|---|---|
| ClinicalAccuracy | To assess thediagnostic ability ofMDW. A multi-center prospectivecohort study wasconducted toclinically validate theperformance ofMonocyte VolumeDistribution Width(MDW) parameter onthe DxH 800hematology analyzer,as an aid in the earlydetection of sepsis inadult patientspresenting to theemergencydepartment (ED). | Class II SpecialControls GuidanceDocument: PremarketNotifications forAutomatedDifferential CellCounters for Immatureor Abnormal BloodCells; Final Guidancefor Industry and FDADecember 4, 2001Statistical Guidanceon Reporting Resultsfrom StudiesEvaluating DiagnosticTests; Final Guidancefor Industry and FDAStaff; March 2007 | CLSI EP12-A2: User Protocolfor Evaluation of QualitativeTest Performance; ApproveGuideline. Second Editionguideline.CLSI EP24-A2: Assessment ofthe Diagnostic Accuracy ofLaboratory Tests UsingReceiver OperatingCharacteristic Curves;Approved Guideline – SecondEdition. 2011. | The study results support theproposed intended use andindications for use. The studyvalidated the two (2) predefinedcut-offs and demonstrated that thelower limit of sensitivity andspecificity were withinacceptance criteria for both cut-offs. However, the studydemonstrated that an MDW cut-off of 20.0 units provided anoptimum diagnostic ability bybalancing the ability to detectpositive patients (sensitivity) andnegative patients (specificity) andthis 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.
§ 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.