(265 days)
The XQ-Series analyzer (XQ-320) is a quantitative multi-parameter automated hematology analyzer intended for in vitro diagnostic use in screening patient populations found in clinical laboratories.
The XQ-320 analyzer classifies and enumerates the following parameters in venous and capillary whole blood samples collected in K2 or K3 EDTA anticoagulant: WBC, RBC, HGB, HCT, MCV, MCH, MCHC, PLT, RDW-SD, RDW-CV, MPV, NEUT%/#, LYMPH%/#, and MXD%/#.
The Sysmex XQ-Series (XQ-320) automated hematology analyzer is a multi-parameter hematology analyzer intended for in vitro diagnostic use in screening patient populations found in clinical laboratories. The XQ-320 analyzer classifies and enumerates whole blood parameters by DC (Direct Current) detection method and non-cyanide HGB analysis method (Colorimetric method) on whole blood samples collected in K2 or K3EDTA anticoagulant. The XQ-320 analyzer consists of one unit which aspirates and dispenses diluent to prepare blood dilutions and analyzes whole blood samples. The operator must mix the sample manually then introduce the sample tube to the aspiration pipette with the cap off, and presses the start switch to execute aspiration and analysis. The XQ-320 analyzer uses a built-in monitor to operate the analyzer and process data.
Here's a breakdown of the acceptance criteria and the study proving the device meets them, based on the provided FDA 510(k) summary for the Sysmex XQ-Series (XQ-320) Automated Hematology Analyzer.
Important Note: This document is a 510(k) summary, which provides a high-level overview of the studies. It does not contain the detailed acceptance criteria for every test or the raw data. The acceptance criteria described are inferred from the statements that "All results met the predefined acceptance criteria" or similar. The "reported device performance" in the table below will be the results stated as meeting those (unspecified) criteria.
1. Table of Acceptance Criteria and Reported Device Performance
The document describes various performance studies. Below is a table summarizing the reported performance, with the understanding that for each, "predefined acceptance criteria" were met. Specific numeric acceptance criteria are generally not provided in this summary.
| Study Type | Acceptance Criteria (Inferred) | Reported Device Performance |
|---|---|---|
| Method Comparison | Regression analysis (slope, intercept, correlation coefficient, bias) and Bland-Altman plots demonstrating agreement with predicate. | WBC: N=378, Range 0.31-98.67, Correlation 0.9994, Slope 0.992 (0.988-0.996 CI), Intercept 0.215 (0.144-0.285 CI) RBC: N=385, Range 1.10-6.78, Correlation 0.9984, Slope 0.970 (0.965-0.976 CI), Intercept 0.107 (0.083-0.130 CI) HGB: N=385, Range 3.2-23.8, Correlation 0.9987, Slope 0.974 (0.969-0.979 CI), Intercept 0.45 (0.39-0.52 CI) HCT: N=379, Range 11.1-59.1, Correlation 0.9965, Slope 0.964 (0.956-0.972 CI), Intercept 0.62 (0.30-0.93 CI) MCV: N=385, Range 52.5-131.6, Correlation 0.9881, Slope 1.005 (0.990-1.021 CI), Intercept -1.98 (-3.43 to -0.53 CI) MCH: N=385, Range 13.1-40.9, Correlation 0.9861, Slope 0.997 (0.981-1.014 CI), Intercept 0.57 (0.08-1.06 CI) MCHC: N=385, Range 22.4-40.2, Correlation 0.8914, Slope 0.880 (0.839-0.922 CI), Intercept 4.83 (3.52-6.13 CI) PLT: N=382, Range 6-941, Correlation 0.9960, Slope 0.989 (0.980-0.998 CI), Intercept -1.9 (-4.9 to 1.0 CI) RDW-SD: N=384, Range 33.6-105.5, Correlation 0.9467, Slope 1.028 (0.995-1.062 CI), Intercept -5.03 (-6.83 to -3.23 CI) RDW-CV: N=385, Range 11.2-26.5, Correlation 0.9645, Slope 1.167 (1.136-1.198 CI), Intercept -3.15 (-3.65 to -2.65 CI) MPV: N=359, Range 8.2-14.5, Correlation 0.9027, Slope 0.912 (0.870-0.954 CI), Intercept 0.40 (-0.05 to 0.86 CI) NEUT#: N=262, Range 0.36-57.75, Correlation 0.9959, Slope 1.020 (1.009-1.031 CI), Intercept -0.176 (-0.299 to -0.052 CI) Lymph#: N=363, Range 0.10-99.84, Correlation 0.9962, Slope 1.012 (1.003-1.021 CI), Intercept 0.109 (-0.005 to 0.222 CI) MXD#: N=262, Range 0.02-3.00, Correlation 0.8525, Slope 1.280 (1.197-1.364 CI), Intercept -0.247 (-0.394 to -0.101 CI) NEUT%: N=262, Range 15.9-96.7, Correlation 0.9600, Slope 1.017 (0.981-1.052 CI), Intercept -2.32 (-4.58 to -0.06 CI) LYMPH%: N=364, Range 0.5-95.2, Correlation 0.9827, Slope 1.031 (1.011-1.051 CI), Intercept 0.18 (-0.56 to 0.91 CI) MXD%: N=262, Range 1.0-18.0, Correlation 0.5933, Slope 1.415 (1.268 to 1.562 CI), Intercept -4.25 (-6.06 to -2.44 CI) |
| Sensitivity & Specificity (Flagging) | Meeting predefined overall percent agreement criteria for detecting abnormal distributional and morphological flags. | Three External Sites: Any Abnormal Distributional Flag: N=237, Sensitivity 89.5% (83.29-94.01 CI), Specificity 75.5% (65.58-83.81 CI), Overall % Agreement 84.0% (78.66-88.40 CI) Any Abnormal Morphological Flag: N=353, Sensitivity 74.5% (67.08-81.06 CI), Specificity 76.0% (69.37-81.89 CI), Overall % Agreement 75.4% (70.52-79.76 CI) Any Abnormal Distributional and/or Abnormal Morphological Flag: N=360, Sensitivity 90.7% (86.36-94.01 CI), Specificity 56.6% (46.99-65.93 CI), Overall % Agreement 80.0% (75.49-84.01 CI) One Internal Site: Any Abnormal Distributional Flag: N=200, Sensitivity 91.4% (83.00-96.45 CI), Specificity 92.4% (86.13-96.48 CI), Overall % Agreement 92.0% (87.33-95.36 CI) Any Abnormal Morphological Flag: N=189, Sensitivity 28.2% (15.00-44.87 CI), Specificity 94.0% (88.92-97.22 CI), Overall % Agreement 80.4% (74.04-85.83 CI) Any Abnormal Distributional and/or Abnormal Morphological Flag: N=200, Sensitivity 83.5% (74.27-90.47 CI), Specificity 91.7% (84.90-96.15 CI), Overall % Agreement 88.0% (82.67-92.16 CI) |
| Precision (Repeatability) | Pooled results meeting predefined acceptance criteria for mean, SD, and %CV across various target levels. | All pooled results met predefined acceptance criteria for all measured parameters (WBC, RBC, HGB, HCT, PLT, MCV, MCH, MCHC, RDW-SD, RDW-CV, MPV, NEUT#/% LYMPH#/% MXD#/%). (Specific values are in the provided tables in the source document, indicating they met the criteria). |
| Reproducibility | All results meeting predefined acceptance criteria for within-run, between-run, between-day, between-site, and total imprecision. | All results met predefined acceptance criteria. (Specific values are in the provided tables in the source document, indicating they met the criteria). |
| Linearity | Meeting predefined acceptance criteria across the claimed linearity ranges. | All results met the predefined acceptance criteria. Claimed linearity ranges provided for WBC, RBC, HGB, HCT, PLT. |
| Carryover | Results determining acceptable levels of carryover. | All results were determined to be acceptable. |
| Interfering Substances Study | No significant interference for specified substances up to certain concentrations. | No significant interference observed for Bilirubin F (40.0 mg/dL), Bilirubin C (40 mg/dL), Hemolytic Hemoglobin (800 mg/dL for HGB, 400 mg/dL for MCHC; 1,000 mg/dL for others), Lipids (0.20 g/dL for HGB, MCH, MCHC; 1.00 g/dL for MPV; 2.00 g/dL for others), High WBC counts (93.53 x 10^3 cells/µL for RBC, HGB, HCT, MCV; 72.08 x 10^3 cells/µL for PLT), High RBC counts (upper measuring range for WBC, RBC, HGB, PLT; 6.64 x 10^6 cells/µL for HCT), High PLT counts (955 x 10^3 cells/µL for WBC, RBC, HGB, HCT, PLT, MPV). Significant chyle interference was observed for MXD# at 720 FTU. |
| LoB, LoD, LoQ | Meeting manufacturer's specifications. | Met manufacturer's specifications. Reported values: WBC (LoB 0.00, LoD 0.03, LoQ 0.17), RBC (LoB 0.00, LoD 0.01, LoQ 0.01), HGB (LoB 0.0, LoD 0.1, LoQ 0.1), HCT (LoB 0.0, LoD 0.1, LoQ 0.1), PLT (LoB 0, LoD 1, LoQ 2). |
| Sample Stability | Supporting the claimed storage conditions in the instructions for use. | Supports 12 hours at room temperature (18-26°C) and 24 hours at refrigerated temperature (2-8°C). |
| Anticoagulant Comparability | Regression analysis and bias estimates meeting acceptance criteria. | Results met the acceptance criteria. |
| Venous vs. Capillary Blood | Regression analysis and bias estimates meeting acceptance criteria. | Results met acceptance criteria. |
| Normal Tubes vs. Micro-collection | Regression analysis and bias estimates meeting acceptance criteria. | Results met acceptance criteria. |
| Whole Blood vs. Predilute Mode | Regression analysis and bias estimates meeting acceptance criteria. | Results met acceptance criteria. |
| Reference Intervals Verification | Normal ranges for adults and pediatric subpopulations consistent with established ranges/literature. | Reference intervals for adults determined acceptable (proposed intervals overlapped 95% CI). Pediatric samples consistent with literature. MXD# and MXD% ranges from predicate (Sysmex pocH-100i) are applicable. |
2. Sample Sizes and Data Provenance
-
Test Set (Method Comparison & Sensitivity/Specificity):
- Method Comparison: 628 unique residual and prospectively collected venous whole blood samples from pediatrics (<21 years) and adults (≥21 years).
- Sensitivity & Specificity (Flagging): Utilized the flagging results from the samples used in the method comparison study (i.e., 628 samples).
- Data Provenance: Three (3) external US clinical sites and one (1) internal site. Samples were from pediatric (<21 years) and adult (≥21 years) subjects, including various disease states. It was a mix of native samples and 17 manipulated samples to span the analytical measuring range. The study was prospective in that samples were "prospectively collected," but also included "residual" samples.
-
Training Set:
- The document does not explicitly mention a "training set" in the context of an AI/algorithm-development process. This device is an automated hematology analyzer, and the performance studies described are for validating the analytical performance of the instrument itself, not an AI model that learns from data.
3. Number of Experts and Qualifications for Ground Truth
- Test Set (Sensitivity & Specificity):
- The ground truth for the flagging study was established by "manual differential counts and peripheral blood smear review by experienced examiners using light microscopy (reference method)."
- The number of experienced examiners is not specified.
- Their specific qualifications (e.g., "radiologist with 10 years of experience") are not detailed beyond "experienced medical technologist" and "experienced examiners."
4. Adjudication Method for the Test Set
- For the sensitivity and specificity study where manual differential counts and blood smear review formed the ground truth, the document does not specify an adjudication method (e.g., 2+1, 3+1). It simply states "by experienced examiners."
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
- No, an MRMC comparative effectiveness study was not done. This device is an automated analyzer, not an AI-assisted diagnostic tool that augments human reader performance in the way a medical imaging AI would. The studies focus on the analytical performance of the instrument itself, often comparing it to a predicate device or manual methods.
6. Standalone (Algorithm Only) Performance
- Yes, the performance evaluated (method comparison, sensitivity/specificity of flagging, precision, etc.) represents the standalone performance of the XQ-320 analyzer as an automated device. Since it's an automated hematology analyzer, its output is the direct performance of the "algorithm" and hardware combination, without a human-in-the-loop performance measurement.
7. Type of Ground Truth Used
- Method Comparison: The ground truth was effectively the measurement results from the predicate device (Sysmex XN-10 analyzer). This is a common approach for demonstrating substantial equivalence for new automated laboratory instruments.
- Sensitivity & Specificity (Flagging): The ground truth was expert consensus / manual review via "manual differential counts and peripheral blood smear review by experienced examiners using light microscopy."
- Other Analytical Studies (Precision, Linearity, LoB/LoD/LoQ, etc.): Ground truth for these is typically established by known concentrations or expected values from control materials or highly characterized samples. For example, linearity uses serial dilutions of a known material.
8. Sample Size for the Training Set
- As noted in point 2, the document does not describe a "training set" in the context of machine learning model development. The studies performed are for validation and verification of an IVD instrument's analytical performance.
9. How the Ground Truth for the Training Set was Established
- Given that no training set for a machine learning model is described, this point is not applicable. For an analytical instrument like this, the "development" data is typically used for calibration, internal testing, and instrument optimization during development, rather than "training" a discrete AI model with labeled data.
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December 21, 2023
Sysmex America, Inc. Yvonne Doswell Sr. Scientist, Regulatory Affairs 577 Aptakisic Road Lincolnshire, Illinois 60069
Re: K230887
Trade/Device Name: Sysmex XQ-Series (XQ-320) Automated Hematology Analyzer Regulation Number: 21 CFR 864.5220 Regulation Name: Automated Differential Cell Counter Regulatory Class: Class II Product Code: GKZ Dated: March 30, 2023 Received: March 31, 2023
Dear Yvonne Doswell:
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 (the 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. 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 available 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. Additional information about changes that may require a new premarket notification are provided in the FDA guidance documents entitled "Deciding When to Submit a 510(k) for a Change to an Existing Device" (https://www.fda.gov/media/99812/download) and "Deciding When to Submit a 510(k) for a Software Change to an Existing Device" (https://www.fda.gov/media/99785/download).
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Your device is also subject to, among other requirements, the Quality System (QS) regulation (21 CFR Part 820), which includes, but is not limited to, 21 CFR 820.30, Design controls; 21 CFR 820.90, Nonconforming product; and 21 CFR 820.100, Corrective and preventive action. Please note that regardless of whether a change requires premarket review. the OS regulation requires device manufacturers to review and approve changes to device design and production (21 CFR 820.30 and 21 CFR 820.70) and document changes and approvals in the device master record (21 CFR 820.181).
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 Part 803) for devices or postmarketing safety reporting (21 CFR Part 4, Subpart B) for combination products (see https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safetyreporting-combination-products); 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 Part 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR Parts 1000-1050.
Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to https://www.fda.gov/medical-device-safety/medical-device-reportingmdr-how-report-medical-device-problems.
For comprehensive regulatory information about mediation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/medicaldevices/device-advice-comprehensive-regulatory-assistance) and CDRH Learn (https://www.fda.gov/training-and-continuing-education/cdrh-learn). 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 (https://www.fda.gov/medical-device-advice-comprehensive-regulatoryassistance/contact-us-division-industry-and-consumer-education-dice) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).
Sincerely,
Min Wu-S
Min Wu, Ph.D. Branch Chief Division of Immunology and Hematology Devices OHT7: Office of In Vitro Diagnostics Office of Product Evaluation and Quality Center for Devices and Radiological Health
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Indications for Use
510(k) Number (if known) K230887
Device Name
Sysmex XQ-Series (XQ-320) Automated Hematology Analyzer
Indications for Use (Describe)
The XQ-Series analyzer (XQ-320) is a quantitative multi-parameter automated hematology analyzer intended for in vitro diagnostic use in screening patient populations found in clinical laboratories.
The XQ-320 analyzer classifies and enumerates the following parameters in venous and capillary whole blood samples collected in K2 or K3 EDTA anticoagulant: WBC, RBC, HGB, HCT, MCV, MCH, MCHC, PLT, RDW-SD, RDW-CV, MPV, NEUT%/#, LYMPH%/#, and MXD%/#.
| 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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5. 510(K) SUMMARY
This summary of 510(k) safety and effectiveness information is being submitted in accordance with the requirements of SMDA 1990 and 21 CFR 807.92.
Submitter's name, address, telephone number, a contact person, and date the summary was prepared:
| Submitter's Name: | Sysmex America, Inc. |
|---|---|
| Submitter's Address: | 577 Aptakisic RoadLincolnshire, IL 60069 |
| Submitter's Contact: | Yvonne DoswellSenior Scientist, Regulatory AffairsE-Mail: doswelly@sysmex.comPhone: (678) 274-8024 |
Date 510(k) Summary Prepared: December 21, 2023
Name of the device, including the trade or proprietary name, the common or usual name, and the classification name:
| Proprietary Name: | Sysmex XQ-Series (XQ-320) Automated Hematology Analyzer |
|---|---|
| Common Name: | Automated Hematology Analyzer |
| Classification Name: | Automated Differential Cell Counter |
| Regulation Description: | Automated Differential Cell Counter |
| Regulation Section: | 21 CFR 864.5220 |
| Device Class: | 2 |
| Product Code: | GKZ |
Related Reagents, Controls and Calibrator:
Product Code: 81GIF CELLPACK (Diluent)
Product Code: 81GGK STROMATOLYSER-WH (Lyse)
Product Code: 81KSA SCS-1000 (Calibrator)
Product Code: 81PPM CELLCLEAN (Cleaning solution)
Product Code: 81JPK EIGHTCHECK-3WP X-TRA (3 Controls)
Predicate Device and 510(k) number: Sysmex XN-Series (XN-10, XN-20) Automated Hematology Analyzer, K112605
Description of the Device:
The Sysmex XQ-Series (XQ-320) automated hematology analyzer is a multi-parameter hematology analyzer intended for in vitro diagnostic use in screening patient populations found in clinical laboratories. The XQ-320 analyzer classifies and enumerates whole blood parameters by DC (Direct Current) detection method and non-cyanide HGB analysis method (Colorimetric
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method) on whole blood samples collected in K2 or K3EDTA anticoagulant. The XQ-320 analyzer consists of one unit which aspirates and dispenses diluent to prepare blood dilutions and analyzes whole blood samples. The operator must mix the sample manually then introduce the sample tube to the aspiration pipette with the cap off, and presses the start switch to execute aspiration and analysis. The XQ-320 analyzer uses a built-in monitor to operate the analyzer and process data.
Statement of Intended Use:
The XQ-Series analyzer (XQ-320) is a quantitative multi-parameter automated hematology analyzer intended for in vitro diagnostic use in screening patient populations found in clinical laboratories.
The XQ-320 analyzer classifies and enumerates the following parameters in venous and capillary whole blood samples collected in K2 or K3 EDTA anticoagulant: WBC, RBC, HCT, MCV, MCH, MCHC, PLT, RDW-SD, RDW-CV, MPV, NEUT%/#, LYMPH%/#, and MXD%/#.
Summary of Comparison of Technological Characteristics:
Table 5-1 compares the similarities and differences between the Sysmex XQ-320 Automated Hematology analyzer with the predicate XN-10 Automated Hematology analyzer.
| Predicate Device:XN-Series (XN-10)K112605 | Subject Device:XQ-Series (XQ-320) | ||
|---|---|---|---|
| Item | Device Similarities | ||
| The XN-Series modules (XN-10, XN-20) are quantitative multi-parameter automated hematology analyzers intended for in vitro diagnostic use in screening patient populations found in clinical laboratories. | The XQ-Series analyzer (XQ-320) is a quantitative multi-parameter automated hematology analyzer intended for in vitro diagnostic use in screening patient populations found in clinical laboratories. | ||
| The XN-Series modules classify and enumerate the following parameters in whole blood: WBC, RBC, HGB, HCT, MCV, MCH, MCHC, PLT, NEUT%/#, LYMPH%/#, MONO%/#, EO%/#, BASO%/#, IG%/#, RDW-CV, RDW-SD, MPV, NRBC%/#, RET%/#, IPF, IRF, RET-He and has a Body Fluid mode for body fluids.The Body Fluid mode enumerates the WBC-BF, RBC-BF, MN%/#, PMN%/# and TC-BF parameters in | The XQ-320 analyzer classifies and enumerates the following parameters in venous and capillary whole blood samples collected in K2 or K3 EDTA anticoagulant: WBC, RBC, HGB, HCT, MCV, MCH, MCHC, PLT, RDW-SD, RDW-CV, MPV, NEUT%/#, LYMPH%/#, and MXD%/#. | ||
| Intended Use | |||
| cerebrospinal fluid (CSF), serousfluids (peritoneal, pleural) andsynovial fluids. Whole blood shouldbe collected in K2 or K3EDTAanticoagulant and, Serous andSynovial fluids in K2EDTAanticoagulant to prevent clotting offluid. The use of anticoagulantswith CSF specimens is neitherrequired nor recommended. | |||
| Specimen Type | Whole Blood collected in K2 orK3EDTA | SAME | |
| Test Principle | Performs hematology analyses usingDC Detection | SAME | |
| Parameters | Whole Blood Mode:WBC, RBC, HGB, HCT, MCV,MCH, MCHC, PLT, NEUT%/#,LYMPH%/#, RDW-CV, RDW-SD,MPV | SAME | |
| Analysis Modes | Manual Analysis Mode[Whole Blood] mode[Pre-Dilute] mode | SAME | |
| SampleAspiration/Fluidic Pathway | Single Pathway | SAME | |
| MeasuringChannels | RBC/PLT, HGB | SAME | |
| Item | Predicate Device:XN-Series (XN-10)K112605 | Subject Device:XQ-Series (XQ-320) | |
| Device Differences | |||
| Specimen Type | Body Fluids Analysis Mode (CSF,Peritoneal, Pleural, and SynovialFluids) | Not Available | |
| Test Principle | Flow cytometry method (using asemiconductor laser) and SLS-hemoglobin method. | DC detection method, Non-cyanidehemoglobin analysis method | |
| Parameters | IG%/#, RET%/#, IPF, IRF, RET-HePLT (PLT-F), NRBC%/#, WBC BF,RBC-BF, MN%/#, PMN%/#, andTC-BF | Not Available | |
| MONO%/#, EO%/#, BASO%/# | MXD%/# (MONO+EO+BASO) | ||
| Reagents | FLUOROCELL WNR (Stain)FLUOROCELL WDF (Stain)FLUOROCELL RET (Stain)FLUOROCELL PLT (Stain) | Not Available | |
| CELLPACK DFL (Diluent)CELLPACK DCL (Diluent) | Not AvailableCELLPACK (Diluent) | ||
| SULFOLYSER® (Lyse) | STROMATOLYSER-WH (Lyse) | ||
| LYSERCELL WNR (Lyse)LYSERCELL WDF (Lyse) | |||
| CELLCLEAN AUTO (Cleaning solution) | |||
| MeasuredChannels | WNR, WPC, WDF, PLT-F, RET | Not Available | |
| WBCDifferential | 5-Part | 3-Part | |
| Controls/Calibrators | Controls:XN-Check -3 levelsXN Check BF - 2 levels | Controls:EIGHTCHECK-3WP_X-TRA 3 levels | |
| Calibrator:XN CAL, XN CAL PF | Calibrator:SCS-1000 | ||
| Sampler Analysis Mode:Sample rack Sampler | Sampler Analysis Mode:Not available | ||
| Analysis Modes | Manual Analysis Mode:[LWBC] ModeBody Fluid Mode | Manual Analysis Mode:Not Available | |
| Whole Blood Mode: 100samples/hour maximum dependingon mode used. | Whole Blood Mode:Approximately 70 samples/hour | ||
| Pre-Dilution mode:Approximately 90 samples/hourmaximum depending on mode used. | Pre-Dilution mode:Approximately 60 samples/hour | ||
| Throughput | Body Fluid Mode:40 samples/hour | Body Fluid Mode:Not Available | |
| SampleAspirationVolumes | Whole Blood Mode: 88 µLPre-Dilution Mode: 70 µLBody Fluid Mode: 88 µL | ||
| Main UnitDimensions(W x D x H | With Sampler (including the sampler(SA-10) 645 x 755 x 855 |
Table 5-1: Comparison of the Predicate XN-10 and the Subject XQ-Series (XQ-320) Automated Hematology Analyzers
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The XQ-320 analyzer Indications for Use statement is similar to the predicate device with minor differences. The XQ-320 analyzer also has similar technological characteristics as the predicate device with minor variation. Both devices measure similar parameters. The data collection and data management software functionality are similar to the predicate device with minor variation.
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The XO-320 analyzer differs from the predicate with a slower throughput and smaller sample aspiration volumes, fewer measuring channels, measurement of specimen types (i.e., body fluids), and fewer parameters measured, however it is very similar in fundamental scientific technology as the predicate device to establish equivalence. In addition. XO-320 control material and calibrator are specific for the XQ-320 analyzer. The XQ-320 analyzer performs a 3-part differential while the XN-10 performs a 5-part differential.
To demonstrate that differences in technological characteristics between the subject device and predicate device do not impact safety and effectiveness, the following clinical performance studies were conducted utilizing the XO-320 analyzer.
Summary of Performance Testing:
Clinical testing was conducted on the XQ-Series (XQ-320) analyzer to show equivalent performance to the XN-10 analyzer. Testing included:
Method Comparison
The method comparison study was conducted based on CLSI EP09c, 3rd edition at three (3) external US clinical sites and one (1) internal site to assess the performance of XQ-320 when compared to the predicate XN-10. A total of 628 unique residual and prospectively collected venous whole blood samples collected in K2EDTA anticoagulant from pediatrics (<21 years) and adult (≥21 years) subjects including a variety of disease states (chronic leukemia (lymphocytic), pathological WBCs, hepatocellular carcinoma, bacterial infection, acute encephalopathy etc.) were enrolled in the study. Of the total samples enrolled, 611 were native, and 17 samples were manipulated to achieve pathological values at the upper and lower analytical measuring range, following CLSI H26-A2 Concentration and Dilution procedures.
Sample demographics from all sites included 172 pediatric subjects (<21 years) and 433 adults (≥21 years) and 23 subjects with age not reported. Of this total, 43.8% were male, 52.2% female and 4.0% with sex not reported.
Samples were tested in singlet within 8 hours of receipt in the testing laboratory and within two hours on both analyzers. Diluted and/or spiked samples were used when native samples were not available to adequately span the full analytical measuring range, but no more than 10% of the total samples tested.
The results of the regression analyses including 95% confidence interval (CI) for the slope and yintercept, mean difference (bias), and percent difference (% bias) were computed for each parameter with results from the XQ-320 analyzer against the results from the Sysmex XN-10 analyzer. Bland-Altman plots were generated to show differences between the two devices for all reportable parameters using the data from all sites combined.
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| Measurand | N | Result Range | CorrelationCoefficient | Slope | 95% ConfidenceInterval | Intercept | 95% ConfidenceInterval |
|---|---|---|---|---|---|---|---|
| WBC(× 103/μL) | 378 | 0.31 to 98.67 | 0.9994 | 0.992 | 0.988 to 0.996 | 0.215 | 0.144 to 0.285 |
| RBC(× 106/μL) | 385 | 1.10 to 6.78 | 0.9984 | 0.970 | 0.965 to 0.976 | 0.107 | 0.083 to 0.130 |
| HGB(g/dL) | 385 | 3.2 to 23.8 | 0.9987 | 0.974 | 0.969 to 0.979 | 0.45 | 0.39 to 0.52 |
| HCT(%) | 379 | 11.1 to 59.1 | 0.9965 | 0.964 | 0.956 to 0.972 | 0.62 | 0.30 to 0.93 |
| MCV(fL) | 385 | 52.5 to 131.6 | 0.9881 | 1.005 | 0.990 to 1.021 | -1.98 | -3.43 to -0.53 |
| MCH(pg) | 385 | 13.1 to 40.9 | 0.9861 | 0.997 | 0.981 to 1.014 | 0.57 | 0.08 to 1.06 |
| MCHC(g/dL) | 385 | 22.4 to 40.2 | 0.8914 | 0.880 | 0.839 to 0.922 | 4.83 | 3.52 to 6.13 |
| PLT(× 103/μL) | 382 | 6 to 941 | 0.9960 | 0.989 | 0.980 to 0.998 | -1.9 | -4.9 to 1.0 |
| RDWSD(fL) | 384 | 33.6 to 105.5 | 0.9467 | 1.028 | 0.995 to 1.062 | -5.03 | -6.83 to -3.23 |
| RDWCV(%) | 385 | 11.2 to 26.5 | 0.9645 | 1.167 | 1.136 to 1.198 | -3.15 | -3.65 to -2.65 |
| MPV(fL) | 359 | 8.2 to 14.5 | 0.9027 | 0.912 | 0.870 to 0.954 | 0.40 | -0.05 to 0.86 |
| NEUT#(× 103/μL) | 262 | 0.36 to 57.75 | 0.9959 | 1.020 | 1.009 to 1.031 | -0.176 | -0.299 to -0.052 |
| Lymph#(× 103/μL) | 363 | 0.10 to 99.84 | 0.9962 | 1.012 | 1.003 to 1.021 | 0.109 | -0.005 to 0.222 |
| MXD#(× 103/μL) | 262 | 0.02 to 3.00 | 0.8525 | 1.280 | 1.197 to 1.364 | -0.247 | -0.394 to -0.101 |
| NEUT%(%) | 262 | 15.9 to 96.7 | 0.9600 | 1.017 | 0.981 to 1.052 | -2.32 | -4.58 to -0.06 |
| LYMPH%(%) | 364 | 0.5 to 95.2 | 0.9827 | 1.031 | 1.011 to 1.051 | 0.18 | -0.56 to 0.91 |
| MXD%(%) | 262 | 1.0 to 18.0 | 0.5933 | 1.415 | 1.268 to 1.562 | -4.25 | -6.06 to -2.44 |
| All Sites Combined - Regression Analysis | ||||
|---|---|---|---|---|
| -- | -- | ------------------------------------------ | -- | -- |
1 N less than 385 were due to sample related errors (masked results [---]).
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Sensitivity and Specificity
Clinical sensitivity/specificity (estimates of agreement) was conducted to evaluate the flagging capabilities of the XO-320 analyzer in identifying/flagging samples with possible abnormalities in the distribution and morphology of white blood cell and platelet parameters, for further investigation and/or review of a blood smear by an experienced medical technologist. The study was conducted in accordance with CLSI H20-A2.
The study was conducted using the flagging results obtained from the samples used in the method comparison study. The flagging results from the XQ-320 analyzers for normal (no flags) and abnormal (flags present) were compared to manual differential counts and peripheral blood smear review by experienced examiners using light microscopy (reference method).
Separate 2x2 tables were constructed to determine sensitivity for both distributional and morphological abnormalities following CLSI EP12-A2. The sample size (N), and number of true positives (TP), false positives (FP), true negative (TN), false negatives (FN), sensitivity, specificity, and overall percent are presented in the following table for the 3 combined external sites and separately for the one (1) internal site.
The study met predefined overall percent agreement criteria and were found to be acceptable.
| Reference Method - Manual Microscopy | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Abnormal FlagCategory | N | TP | FP | TN | FN | Sensitivity(95% CI) | Specificity(95% CI) | Overall %Agreement | |
| SysmexXQ-320 | Any AbnormalDistributionalFlag | 237 | 128 | 23 | 71 | 15 | 89.5(83.29, 94.01) | 75.5(65.58, 83.81) | 84.0(78.66, 88.40) |
| Any AbnormalMorphologicalFlag | 353 | 120 | 46 | 146 | 41 | 74.5(67.08, 81.06) | 76.0(69.37, 81.89) | 75.4(70.52, 79.76) | |
| Any AbnormalDistributionaland/or AbnormalMorphologicalFlag | 360 | 224 | 49 | 64 | 23 | 90.7(86.36, 94.01) | 56.6(46.99, 65.93) | 80.0(75.49, 84.01) |
Distributional and Morphological Abnormal Flagging Summary - Three External Clinical Sites
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| Reference Method - Manual Microscopy | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| AbnormalFlag Category | N | TP | FP | TN | FN | Sensitivity(95% CI) | Specificity(95% CI) | Overall %Agreement | |
| SysmexXQ-320 | Any AbnormalDistributionalFlag | 200 | 74 | 9 | 110 | 7 | 91.4(83.00, 96.45) | 92.4(86.13, 96.48) | 92.0(87.33, 95.36) |
| Any AbnormalMorphologicalFlag | 189 | 11 | 9 | 141 | 28 | 28.2(15.00, 44.87) | 94.0(88.92, 97.22) | 80.4(74.04, 85.83) | |
| Any AbnormalDistributionaland/orAbnormalMorphologicalFlag | 200 | 76 | 9 | 100 | 15 | 83.5(74.27, 90.47) | 91.7(84.90, 96.15) | 88.0(82.67, 92.16) |
Distributional and Morphological Abnormal Flagging Summary - One Internal Site
Precision (Repeatability)
Repeatability studies were performed across three XQ-320 analyzers in accordance with the CLSI H26-A2, Validation, Verification, and Quality Assurance of Automated Hematology Analyzers; Approved Standard, Second Edition, to evaluate the precision (repeatability) of all claimed parameters on the XQ-320 analyzer.
The studies were conducted using residual K2EDTA venous whole blood samples targeting medical decision levels, the normal range and upper and of the analytical measuring range of direct measured parameters (WBC, RBC, HCT and PLT). All samples were tested in replicates of ten and the mean, standard deviation (SD), and coefficient of variation were calculated for each parameter.
All pooled results met the predefined acceptance criteria and were determined to be acceptable.
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| Measurand | Sample level | N replicates | Interval | Mean | Pooled SD | Pooled %CV |
|---|---|---|---|---|---|---|
| WBC (x 103/uL) | MDL | 30 | 0.67 - 0.84 | 0.75 | 0.04 | 4.45 |
| WBC (x 103/uL) | Low | 30 | 1.21 - 1.91 | 1.64 | 0.04 | 2.44 |
| WBC (x 103/uL) | Normal | 30 | 9.81 - 10.65 | 10.28 | 0.15 | 1.45 |
| WBC (x 103/uL) | High | 30 | 70.97 - 93.53 | 83.94 | 0.61 | 0.73 |
| RBC (x 106/uL) | Low | 30 | 2.03 - 2.85 | 2.53 | 0.02 | 0.99 |
| RBC (x 106/uL) | Normal | 30 | 4.41 - 4.94 | 4.70 | 0.04 | 0.84 |
| RBC (x 106/uL) | High | 30 | 6.16 - 6.80 | 6.43 | 0.07 | 1.05 |
| HGB (g/dL) | Low | 30 | 6.1 - 6.9 | 6.49 | 0.06 | 0.92 |
| HGB (g/dL) | Normal | 30 | 13.5 - 15.5 | 14.36 | 0.11 | 0.79 |
| HGB (g/dL) | High | 30 | 17.4 - 19.2 | 18.05 | 0.07 | 0.38 |
| HCT(%) | Low | 30 | 18.2 - 23.0 | 20.50 | 0.24 | 1.16 |
| HCT(%) | Normal | 30 | 40.2 - 44.6 | 42.10 | 0.39 | 0.93 |
| HCT(%) | High | 30 | 52.3 - 58.7 | 54.99 | 0.48 | 0.87 |
| PLT (103/μL) | MDL | 30 | 9 - 26 | 14.33 | 2.60 | 17.11 |
| PLT (103/μL) | Low | 30 | 30 - 44 | 37.10 | 3.06 | 8.28 |
| PLT (103/μL) | Normal | 30 | 216 - 311 | 271.57 | 6.50 | 2.46 |
| PLT (103/μL) | High | 30 | 618 - 982 | 815.30 | 13.02 | 1.67 |
| MCV (fL) | Low | 30 | 66.4 - 88.0 | 77.73 | 0.26 | 0.33 |
| MCV (fL) | Normal | 30 | 82.2 - 91.1 | 86.50 | 0.43 | 0.50 |
| MCV (fL) | High | 30 | 102.9 - 112.6 | 108.77 | 0.52 | 0.47 |
| MCH (pg) | Low | 30 | 20.3 - 25.7 | 23.50 | 0.30 | 1.26 |
| MCH (pg) | Normal | 30 | 26.4 - 31.0 | 28.33 | 0.29 | 1.02 |
| MCH (pg) | High | 30 | 30.7 - 41.8 | 35.73 | 0.54 | 1.45 |
| MCHC (g/dL) | Low | 30 | 26.2 - 28.9 | 27.80 | 0.36 | 1.31 |
| Normal | 30 | 28.6 - 32.2 | 30.87 | 0.31 | 1.00 | |
| High | 30 | 32.1 - 36.9 | 34.50 | 0.47 | 1.35 | |
| RDW-SD (fL) | Low | 30 | 33.7 - 45.5 | 38.87 | 0.64 | 1.67 |
| RDW-SD (fL) | Normal | 30 | 41.1 - 58.2 | 47.77 | 0.76 | 1.60 |
| RDW-SD (fL) | High | 30 | 72.6 - 96.0 | 81.40 | 1.46 | 1.80 |
| Measurand | Samplelevel | Nreplicates | Interval | Mean | Pooled SD | Pooled %CV |
| RDW-CV (%) | Low | 30 | 9.5 - 12.6 | 11.20 | 0.58 | 1.04 |
| Normal | 30 | 13.1 - 15.5 | 14.37 | 0.67 | 1.17 | |
| High | 30 | 17.2 - 29.9 | 22.60 | 0.69 | 1.13 | |
| MPV (fL) | Low | 30 | 8.2-8.8 | 8.53 | 0.95 | 1.75 |
| Normal | 30 | 8.3 - 10.4 | 9.50 | 1.10 | 2.01 | |
| High | 30 | 11.1 - 13.0 | 11.97 | 1.40 | 2.50 | |
| NEUT (x 103/uL) | Low | 30 | 0.39 - 1.37 | 0.91 | 3.99 | 7.91 |
| Normal | 30 | 1.21 - 8.70 | 4.69 | 1.85 | 3.56 | |
| High | 30 | 3.36 - 41.53 | 16.38 | 1.58 | 2.85 | |
| NEUT (%) | Low | 30 | 21.0 - 57.2 | 38.40 | 4.88 | 7.16 |
| Normal | 30 | 45.9 - 86.2 | 61.20 | 1.91 | 2.50 | |
| High | 30 | 72.5 - 95.9 | 84.83 | 2.47 | 2.72 | |
| LYMPH (x 103/uL) | Low | 30 | 0.34 - 0.73 | 0.49 | 0.01 | 4.31 |
| Normal | 30 | 0.67 - 48.39 | 16.47 | 0.40 | 3.15 | |
| High | 30 | 2.23 - 75.29 | 26.63 | 0.33 | 2.29 | |
| LYMPH (%) | Low | 30 | 3.4 - 9.9 | 5.70 | 0.37 | 5.95 |
| Normal | 30 | 19.8 - 32.9 | 27.97 | 0.85 | 3.10 | |
| High | 30 | 61.0 - 87.6 | 77.67 | 0.71 | 0.99 | |
| MXD (x 103/uL) | Low | 30 | 0.39 - 1.70 | 0.81 | 0.08 | 10.60 |
| Normal | 30 | 0.59 - 2.39 | 1.27 | 0.15 | 13.11 | |
| High | 30 | 0.39 - 15.45 | 5.85 | 0.27 | 7.47 | |
| MXD (%) | Low | 30 | 2.6 - 14.5 | 6.87 | 0.65 | 10.11 |
| Normal | 30 | 6.7 - 19.2 | 11.67 | 1.60 | 13.00 | |
| High | 30 | 10.0 - 31.6 | 22.03 | 1.55 | 7.17 |
Precision Repeatability Study
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Reproducibilitv
Reproducibility studies were performed at three external US sites to evaluate the within run, between run, between day, between site, and total imprecision of all claimed parameters on the XQ-320 analyzer in accordance with the CLSI EP05-A3 approved guidelines.
Testing was conducted by 2-4 operators at each site using 3 levels of EIGHTCHECK-3WP X-TRA whole blood control material. Each level was run in triplicate, twice a day for 5 days using a single calibration and reagent lot across 3 sites for a total of 90 results per control level.
The results were analyzed by analysis of variance (ANOVA) method. The SD and %CV were calculated for within-run, between-run, between-day, between-site and total imprecision for each control level and presented in the table below. All results met the predefined acceptance criteria and were determined to be acceptable.
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| XQ-320All Combined Sites | Within Run | Between Run | Between Day | BetweenSite | Total | ||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Measurand | Control | ||||||||||||
| (unit) | Level | N | Mean | SD | %CV | SD | %CV | SD | %CV | SD | %CV | SD | %CV |
| Low | 90 | 3.42 | 0.000 | 0.00 | 0.064 | 1.87 | 0.042 | 1.23 | 0.000 | 0.00 | 0.077 | 2.24 | |
| WBC | Normal | 90 | 7.38 | 0.000 | 0.00 | 0.120 | 1.60 | 0.050 | 0.68 | 0.056 | 0.75 | 0.140 | 1.89 |
| (x 103/uL) | High | 90 | 19.3 | 0.040 | 0.21 | 0.190 | 0.97 | 0.100 | 0.54 | 0.110 | 0.59 | 0.250 | 1.28 |
| Low | 90 | 2.45 | 0.000 | 0.00 | 0.034 | 1.39 | 0.014 | 0.56 | 0.000 | 0.00 | 0.037 | 1.49 | |
| RBC | Normal | 90 | 4.59 | 0.000 | 0.00 | 0.047 | 1.01 | 0.023 | 0.51 | 0.000 | 0.00 | 0.052 | 1.13 |
| (x 106/uL) | High | 90 | 5.58 | 0.000 | 0.00 | 0.065 | 1.16 | 0.027 | 0.48 | 0.000 | 0.00 | 0.070 | 1.25 |
| Low | 90 | 6.61 | 0.00 | 0.00 | 0.05 | 0.77 | 0.06 | 0.92 | 0.04 | 0.71 | 0.09 | 1.40 | |
| HGB | Normal | 90 | 13.3 | 0.04 | 0.33 | 0.04 | 0.36 | 0.05 | 0.39 | 0.12 | 0.90 | 0.15 | 1.09 |
| (g/dL) | High | 90 | 17.3 | 0.00 | 0.00 | 0.08 | 0.49 | 0.06 | 0.39 | 0.11 | 0.61 | 0.15 | 0.88 |
| Low | 90 | 18.5 | 0.00 | 0.00 | 0.26 | 1.39 | 0.09 | 0.53 | 0.11 | 0.62 | 0.30 | 1.61 | |
| HCT | Normal | 90 | 37.4 | 0.00 | 0.00 | 0.40 | 1.06 | 0.14 | 0.37 | 0.22 | 0.59 | 0.47 | 1.27 |
| %) | High | 90 | 48.5 | 0.19 | 0.39 | 0.53 | 1.10 | 0.05 | 0.11 | 0.24 | 0.50 | 0.62 | 1.28 |
| Low | 90 | 75.3 | 0.00 | 0.00 | 0.37 | 0.49 | 0.37 | 0.48 | 0.36 | 0.48 | 0.64 | 0.84 | |
| MCV | Normal | 90 | 81.4 | 0.00 | 0.00 | 0.30 | 0.37 | 0.45 | 0.55 | 0.41 | 0.50 | 0.67 | 0.83 |
| (fL) | High | 90 | 86.9 | 0.07 | 0.08 | 0.33 | 0.38 | 0.30 | 0.34 | 0.41 | 0.47 | 0.61 | 0.70 |
| Low | 90 | 27.0 | 0.00 | 0.00 | 0.43 | 1.59 | 0.13 | 0.48 | 0.25 | 0.92 | 0.51 | 1.90 | |
| MCH | Normal | 90 | 29.0 | 0.00 | 0.00 | 0.29 | 1.01 | 0.07 | 0.27 | 0.28 | 0.98 | 0.42 | 1.43 |
| (pg) | High | 90 | 31.0 | 0.12 | 0.40 | 0.34 | 1.09 | 0.00 | 0.00 | 0.21 | 0.67 | 0.42 | 1.34 |
| Low | 90 | 35.8 | 0.00 | 0.00 | 0.56 | 1.57 | 0.33 | 0.93 | 0.51 | 1.43 | 0.83 | 2.32 | |
| MCHC | Normal | 90 | 35.6 | 0.02 | 0.08 | 0.35 | 1.00 | 0.23 | 0.65 | 0.52 | 1.46 | 0.67 | 1.89 |
| (g/dL) | High | 90 | 35.7 | 0.25 | 0.71 | 0.36 | 1.02 | 0.00 | 0.00 | 0.42 | 1.16 | 0.61 | 1.70 |
| Low | 90 | 78 | 0.00 | 0.00 | 4.31 | 5.48 | 1.80 | 2.29 | 1.05 | 1.33 | 4.79 | 6.09 | |
| PLT | Normal | 90 | 238 | 0.00 | 0.00 | 6.99 | 2.94 | 2.68 | 1.13 | 2.03 | 0.85 | 7.76 | 3.26 |
| (x 103/uL) | High | 90 | 560 | 0.00 | 0.00 | 13.80 | 2.47 | 8.94 | 1.60 | 5.49 | 0.98 | 17.30 | 3.10 |
| Low | 90 | 26.1 | 0.00 | 0.00 | 0.52 | 1.99 | 0.24 | 0.93 | 0.51 | 1.96 | 0.77 | 2.95 | |
| RDW-SD | Normal | 90 | 28.3 | 0.00 | 0.00 | 0.47 | 1.65 | 0.26 | 0.91 | 0.22 | 0.78 | 0.58 | 2.04 |
| (fL) | High | 90 | 30.8 | 0.24 | 0.78 | 0.37 | 1.22 | 0.12 | 0.40 | 0.62 | 2.00 | 0.77 | 2.50 |
| Low | 90 | 9.41 | 0.00 | 0.00 | 0.26 | 2.75 | 0.20 | 2.11 | 0.08 | 0.92 | 0.34 | 3.58 | |
| RDW-CV | Normal | 90 | 8.77 | 0.00 | 0.00 | 0.18 | 2.01 | 0.24 | 2.77 | 0.00 | 0.00 | 0.30 | 3.42 |
| %) | High | 90 | 8.58 | 0.00 | 0.00 | 0.17 | 2.02 | 0.20 | 2.28 | 0.08 | 0.94 | 0.27 | 3.19 |
| Low | 90 | 9.08 | 0.00 | 0.00 | 0.16 | 1.81 | 0.11 | 1.20 | 0.16 | 1.78 | 0.26 | 2.81 | |
| MPV | Normal | 90 | 8.90 | 0.00 | 0.00 | 0.09 | 1.10 | 0.01 | 0.21 | 0.18 | 2.07 | 0.21 | 2.36 |
| (fL) | High | 90 | 8.84 | 0.00 | 0.00 | 0.10 | 1.15 | 0.05 | 0.59 | 0.18 | 2.02 | 0.21 | 2.39 |
| Low | 90 | 2.40 | 0.000 | 0.00 | 0.075 | 3.13 | 0.008 | 0.32 | 0.021 | 0.89 | 0.078 | 3.27 | |
| NEUT | Normal | 90 | 4.20 | 0.046 | 1.10 | 0.100 | 2.44 | 0.000 | 0.00 | 0.050 | 1.19 | 0.120 | 2.93 |
| (x 103/uL) | High | 90 | 9.10 | 0.000 | 0.00 | 0.200 | 2.15 | 0.000 | 0.00 | 0.093 | 1.02 | 0.220 | 2.38 |
| Low | 90 | 70.1 | 0.00 | 0.00 | 1.75 | 2.50 | 0.40 | 0.57 | 0.37 | 0.53 | 1.84 | 2.62 | |
| NEUT% | Normal | 90 | 57.0 | 0.24 | 0.43 | 1.15 | 2.01 | 0.00 | 0.00 | 0.21 | 0.36 | 1.19 | 2.09 |
| (%) | High | 90 | 47.3 | 0.00 | 0.00 | 0.90 | 1.90 | 0.19 | 0.41 | 0.31 | 0.65 | 0.97 | 2.05 |
| XQ-320All Combined Sites | Within Run | Between Run | Between Day | BetweenSite | Total | ||||||||
| Measurand(unit) | ControlLevel | N | Mean | SD | %CV | SD | %CV | SD | %CV | SD | %CV | SD | %CV |
| LYMPH(x 103/uL) | Low | 90 | 0.65 | 0.009 | 1.34 | 0.031 | 4.83 | 0.015 | 2.25 | 0.000 | 0.00 | 0.036 | 5.49 |
| LYMPH(x 103/uL) | Normal | 90 | 2.26 | 0.000 | 0.00 | 0.072 | 3.19 | 0.022 | 0.96 | 0.000 | 0.00 | 0.075 | 3.33 |
| LYMPH(x 103/uL) | High | 90 | 6.96 | 0.000 | 0.00 | 0.130 | 1.90 | 0.076 | 1.10 | 0.059 | 0.85 | 0.160 | 2.35 |
| LYMPH%(%) | Low | 90 | 19.0 | 0.00 | 0.00 | 0.86 | 4.54 | 0.24 | 1.24 | 0.00 | 0.00 | 0.89 | 4.70 |
| LYMPH%(%) | Normal | 90 | 30.6 | 0.00 | 0.00 | 0.83 | 2.70 | 0.00 | 0.00 | 0.30 | 0.98 | 0.88 | 2.87 |
| LYMPH%(%) | High | 90 | 36.1 | 0.00 | 0.00 | 0.55 | 1.51 | 0.14 | 0.40 | 0.21 | 0.58 | 0.60 | 1.67 |
| MXD(x 103/uL) | Low | 90 | 0.37 | 0.000 | 0.00 | 0.060 | 16.20 | 0.000 | 0.00 | 0.012 | 3.10 | 0.061 | 16.50 |
| MXD(x 103/uL) | Normal | 90 | 0.91 | 0.000 | 0.00 | 0.079 | 8.60 | 0.020 | 2.16 | 0.011 | 1.23 | 0.082 | 8.95 |
| MXD(x 103/uL) | High | 90 | 3.20 | 0.000 | 0.00 | 0.170 | 5.32 | 0.000 | 0.00 | 0.000 | 0.00 | 0.170 | 5.32 |
| MXD%(%) | Low | 90 | 10.9 | 0.00 | 0.00 | 1.76 | 16.20 | 0.00 | 0.00 | 0.40 | 3.69 | 1.81 | 16.60 |
| MXD%(%) | Normal | 90 | 12.4 | 0.23 | 1.84 | 1.02 | 8.27 | 0.00 | 0.00 | 0.00 | 0.00 | 1.05 | 8.47 |
| MXD%(%) | High | 90 | 16.6 | 0.00 | 0.00 | 0.89 | 5.35 | 0.00 | 0.00 | 0.03 | 0.18 | 0.89 | 5.35 |
All Sites Combined – Reproducibility Study
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Linearity
Linearity studies were performed in accordance with the CLSI EP06-ED2, Evaluation of Linearity of Quantitative Measurement Procedures; 2020 using WRP CHECK control material.
Testing was conducted at one internal site across three XQ-320 analyzers, using a single calibrator and reagent lot. System diluent (CELLPACK) was used to create serial dilutions of sample (WRP CHECK control material) concentrations which spanned the full measurement range of all direct measured parameters (WBC, RBC, HGB, HCT and PLT). A minimum of seven and maximum of 11 sample dilutions and three replicate measurements of each sample dilution were tested for each parameter.
All results met the predefined acceptance criteria and were determined to be acceptable.
| Claimed Linearity Specifications | |
|---|---|
| Parameter | Linearity range |
| WBC(x 103/μL) | 0.20 – 99.90 |
| RBC(x 106/μL) | 0.01 - 7.00 |
| HGB(g/dL) | 0.1 - 25.0 |
| HCT(%) | 0.2 - 60.0 |
| PLT(x 103/μL) | 5 - 999 |
Claimed Linearity Specificatio
{15}------------------------------------------------
Carryover
Carryover on the XQ-320 analyzer was performed in accordance with CLSI H26-A2 Validation, Verification, and Quality Assurance of Hematology Analyzers; Approved Standard, Second Edition, 2010 using venous whole blood K2EDTA samples.
Testing was conducted at three US sites by testing samples with high counts in replicates of three followed by samples with low counts for targeted WBC, RBC, HCT and PLT parameters. Three sets of carryover sequences were run for each parameter.
All results were determined to be acceptable.
Interfering Substances Study
Interfering substances studies were conducted in accordance with CLSI EP07-Ed3 guideline for Bilirubin F, Bilirubin C, Chyle, Hemolytic Hemoglobin, Lipids interferents to determine the concentration of well-known interferences that impact parameters on the XQ-320 analyzer.
In addition, interference by abnormal specimen studies were performed to characterize the susceptibility of the XQ-320 device to three potential interfering conditions due elevated WBCs, elevated RBCs, and elevated PLTs.
All results met the predefined acceptance criteria and were determined to be acceptable.
{16}------------------------------------------------
| Interferent | Conclusion |
|---|---|
| Bilirubin F | There was no significant Bilirubin F interference up to a concentration of 40.0 mg/dL for all parameters. |
| Bilirubin C | There was no significant Bilirubin C interference up to a concentration of 40 mg/dL for all parameters. |
| Chyle | There was no significant Chyle interference up to a concentration of 2,880 FTU (Formazine Turbidity Unit) for WBC, up to a concentration of 1,440 FTU for NEUT%, LYMPH%, and MXD% and up to a concentration of 720 FTU for LYMPH#. There was no significant Chyle interference up to a concentration of 3,600 FTU for the other parameters. Significant chyle interference was observed for MXD# at a concentration of 720 FTU. |
| Hemolytic Hemoglobin | There was no significant Hemolysis interference up to a concentration of 800 mg/dL for HGB and 400 mg/dL for MCHC. For the other parameters, no significant interference was observed up to a concentration of 1,000 mg/dL. |
| Lipids | There was no significant Lipid interference up to a concentration of 0.20 g/dL for HGB, MCH, and MCHC and 1.00 g/dL for MPV. There was no significant Lipid interference up to a concentration of 2.00 g/dL for the other parameters. |
| High white blood cell counts | There was no significant WBC interference up to a concentration of 93.53 x 103 cells/µL for RBC, HGB, HCT and MCV.There was no significant WBC interference up to a concentration of 72.08 x 103 cells/µL for PLT. |
| High red blood cell counts | There was no interference from high RBCs at the upper measuring range in measuring WBC, RBC, HGB, and PLT.There was no significant RBC interference up to a concentration of 6.64 x 106 cells/µL for HCT. |
| High platelet counts | There was no significant PLT interference up to a concentration of 955 x 103 cells/µL for WBC, RBC, HGB, HCT, PLT, and MPV |
Limits of Blank, Detection, and Quantitation (LoB, LoD, and LoQ)
The Limit of Blank (LoB), Limit of Detection (LoD, and the Limit of Quantitation (LoQ) were established for the direct measured WBC, RBC, HGB, HCT and PLT parameters on the XQ-320 analyzer in accordance with CLSI EP17-A2, Evaluation of Detection Capability for Clinical Laboratory Measurement Procedures; Approved Guideline-Second Edition. 2012.
Testing was conducted over a minimum of three days using 2 reagent lots, a minimum of 4 samples per day with a minimum of four replicates per sample.
The LoB, LoD and LoO results met the manufacturer's specifications shown in the table below.
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| Parameter | LoB(N=120) | LoD(N=120) | LoQ(N=120) |
|---|---|---|---|
| WBC (x 103/μL) | 0.00 | 0.03 | 0.17 |
| RBC (x 106/μL) | 0.00 | 0.01 | 0.01 |
| HGB (g/dL) | 0.0 | 0.1 | 0.1 |
| HCT (%) | 0.0 | 0.1 | 0.1 |
| PLT (x 103/μL) | 0 | 1 | 2 |
Limit of Blank, Detection and Quantitation
Sample Stability
The evaluation of whole blood sample stability was conducted at one site using twenty (10 normal and 10 abnormal) residual K2EDTA anticoagulated whole blood samples. Samples were split into two sets room temperature (18-26°C) and refrigerated temperature (18-26°C).
Room temperature samples were tested in singlet at baseline or zero (0) time, 4, 8, 12 and 13 hours and refrigerated samples were tested at baseline or zero (0) time. 8, 12, 24 and 25 hours in singlet.
Whole blood sample stability supports storage condition: 12 hours at room temperature (18-26°C) and 24 hours at refrigerated temperature (2-8°C) provided in the instructions for use labeling.
Anticoagulant Comparability (K2EDTA vs. K3EDTA)
Comparability between K2EDTA vs. K3EDTA anticoagulated whole blood samples on the XQ-320 analyzer was conducted using a total of 53 paired (K2 and K3EDTA) whole blood samples collected from consented adult (>21 years) donors.
Each sample was run in singlet within 8 hours of collection. The results from the K2EDTA whole blood samples were compared to the corresponding results of the K3EDTA sample for the same donor.
The results of the regression analysis and bias estimates between K2EDTA and K3EDTA anticoagulated whole blood samples met the acceptance criteria.
Venous Whole Blood vs. Capillary Whole Blood (K2EDTA)
Comparability between venous whole blood and capillary whole blood samples on the XQ-320 analyzer was conducted using forty-two paired venous whole blood and capillary whole blood samples (K2EDTA) drawn from consented adult (>21 years) donors.
Each sample was run in singlet within 8 hours of collection. The venous whole blood sample results were compared to the corresponding results of the capillary sample for the same donor.
The results of the regression analysis and bias estimates between venous and capillary K2EDTA whole blood samples met acceptance criteria.
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Whole Blood K2EDTA Normal Tubes vs. Micro-collection Tube
K2EDTA tubes and micro-collection tubes without anticoagulant were performed to determine the presence or absence of matrix effect between the sample tubes on the XQ-320 analyzer.
This study used a total of 183 residual K2EDTA (4 mL tubes) whole blood samples with analyte concentrations representative of patient samples, across medical decision levels, and to the extent possible of the full analytical measuring range. Whole blood K2EDTA normal tubes were premixed and run in singlet. Within two hours of analysis of the K2EDTA normal tubes, the samples were remixed, then transferred to micro-collection tubes without anticoagulant additive, then analyzed in singlet.
The results from the K2EDTA whole blood samples were compared to the corresponding results of the micro-collection sample tube for the same patient sample. The results of the regression analysis and bias estimates between the whole blood normal K2EDTA to micro-tube comparison samples met acceptance criteria.
Whole Blood K2EDTA Mode vs. Pre-dilute Mode
Comparability between the whole blood and predilute mode on the XQ-320 analyzer was performed using 35 residual K2EDTA anticoagulated whole blood samples. The K2EDTA whole blood samples were premixed from end to end by gentle inversion, then run in the whole blood mode with caps off. Following the analysis of the whole blood samples, a 1:7 predilute sample was prepared for each whole blood sample by adding 120 µL of system diluent (CELLPACK) and 20 uL of whole blood into plain micro-collection tubes. The prediluted samples were thoroughly mixed by gentle inversion and run in the predilute mode of the XQ-320 analyzer with caps off. The results from the predilute mode are automatically multiplied by 7 before results are displayed, therefore no additional calculation is required. The results from the K2EDTA whole blood samples were compared to the corresponding results of the prediluted sample for the same patient sample. The results of the regression analysis and bias estimates between the whole blood and predilute mode samples met acceptance criteria.
Reference Intervals
Verification of adult and pediatric reference intervals was conducted on the XQ-320 analyzer to demonstrate comparability of whole blood reference intervals for an adult population (>21 years) to the ranges established for the Sysmex pocH-100i (K032677) and pediatric population (birth to <21 years) to ranges based on literature reference intervals. Verification was conducted according to CLSI EP28-A3c.
The verification of adult reference ranges was conducted by comparing sample results that were reported as 'Negative' judgment (without flags) from apparently normal, healthy adult subjects in the method comparison study to previously established reference intervals to determine if the ranges are applicable for use with the XQ-320 analyzer.
Results from pediatric samples enrolled in the method comparison study were compared to literature reference intervals for acceptable use with the XQ-320.
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The reference ranges were previously established for the Sysmex pocH-100i. which include MXD# and MXD%, and these ranges are applicable for use with the XO-320 analyzer. Reference intervals for adults were established by evaluating 99 unique male and female (43 male and 56 female) whole blood samples collected from generally healthy, consenting donors, >21 years of age to verify normal reference ranges.
Reference intervals for adults were determined to be acceptable if the proposed reference intervals overlapped the 95% confidence intervals (lower and upper limit) of the dataset.
The results from 226 pediatric subjects including each pediatric subpopulations: 34 neonates (birth-1 month); 63 infants (>1 month-2 years); 63 children (>2 years-12 years); and 66 adolescents (>12 years-21 years) were compared to literature reference intervals.
Conclusions:
The XQ-Series (XQ-320) Automated Hematology analyzer and its predicate device, XN-10 Automated Hematology analyzer (K112605), have similar Indications for Use, fundamental technology, and principles of operation. Performance, verification, and validation testing were conducted to characterize the performance of the XQ-320 analyzer using predetermined acceptance criteria. Results of this testing have documented that the XQ-320 analyzer is substantially equivalent to the XN-10 analyzer. The differences in the XQ-320 analyzer and the predicate device (XN-10 analyzer) do not raise any questions regarding safety and effectiveness.
§ 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.”