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The XR-Series module (XR-10) is a quantitative multi-parameter automated hematology analyzer intended for in vitro diagnostic use in screening patient populations found in clinical laboratories.

The XR-Series module classifies and enumerates the following parameters in whole blood: WBC, RBC, HGB, HCT, MCV, MCH, MCHC, PLT (PLT-I, PLT-F), NEUT%/#, LYMPH%/#, MONO%/#, EO%/#, BASO%/#, IG%/#, RDW-CV, RDW-SD, MPV, NRBC%/#, RET%/#, IPF, 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 cerebrospinal fluid (CSF), serous fluids (peritoneal, pleural) and synovial fluids. Whole blood should be collected in K2EDTA or K3EDTA anticoagulant, and serous and synovial fluids in K2EDTA anticoagulant to prevent clotting of fluid. The use of anticoagulants with CSF specimens is neither required nor recommended.

The Sysmex XR-Series module (XR-10) is a quantitative multi-parameter hematology analyzer intended to perform tests on whole blood samples collected in K2 or K3EDTA and body fluids (pleural, peritoneal and synovial) collected in K2EDTA anticoagulant. The analyzers can also perform tests on CSF, which should not be collected in any anticoagulant. The XR-Series analyzer consist of four principal units: (1) One Main Units (XR-10) which aspirates, dilutes, mixes, and analyzes blood and body fluid samples; (2) Two Auto Sampler Units (SA-10, SA-01) which supply samples to the Main Unit automatically; (3) IPU (Information Processing Unit) which processes data from the Main Unit and provides the operator interface with the system; (4) Pneumatic Unit which supplies pressure and vacuum from the Main Unit.

This document describes the acceptance criteria and the studies conducted to prove that the Sysmex XR-Series (XR-10) Automated Hematology Analyzer meets these criteria, demonstrating substantial equivalence to its predicate device, the Sysmex XN-20.

1. Table of Acceptance Criteria and Reported Device Performance

The FDA 510(k) clearance letter does not explicitly present a neatly formatted table of acceptance criteria alongside the reported performance for all parameters. Instead, it describes various performance studies (Precision, Linearity, Analytical Specificity/Interferences, Sample Stability, Detection Limit, Carry-Over, Comparison Studies, Matrix Studies, Bridging Studies, Clinical Studies, and Expected Values/Reference Range) and states that the XR-10 met "manufacturer's specifications or predefined acceptance criteria requirements" for each.

However, based on the provided data, we can infer some general acceptance criteria, particularly from the method comparison study which uses correlation coefficient (r) and percent bias (%Bias) as metrics. The clinical sensitivity and specificity tables also present implied acceptance criteria based on the demonstrated performance.

Inferred Acceptance Criteria & Reported Performance (Selection of Key Metrics)

2. Sample Size Used for the Test Set and Data Provenance

• Test Set Sample Size & Provenance:
  • Precision (Repeatability - Whole Blood): Residual K2EDTA whole blood samples for 10 replicates for target values, and three samples for other parameters. This was across three US clinical sites (Site 01, 05, 24).
  • Precision (Reproducibility - Whole Blood): XN CHECK whole blood control material, 90 results per control level (3 levels x 3 replicates x 2 runs x 5 days). Conducted at three US clinical sites.
  • Precision (Body Fluid): Residual peritoneal, pleural, and synovial fluid samples (K2EDTA) and CSF (no anticoagulant) for 10 replicates for target values. Conducted at three US clinical sites.
  • Linearity (Whole Blood & Body Fluid): Minimum of seven sample dilutions. Performed at one internal site.
  • Analytical Specificity/Interferences: Whole blood K2EDTA samples from donors. Number of samples not specified, but collected for this study purpose.
  • Sample Stability (Whole Blood): 8 unique leftover samples and 12 prospectively collected K2EDTA venous whole blood samples (20 samples total). Conducted at one internal site.
  • Sample Stability (Body Fluid): 12 unique de-identified leftover body fluid samples (3-CSF, 3-peritoneal, 3-pleural, 3-synovial). Conducted at 1 external site.
  • Detection Limit: Four blank samples and four low concentration samples for each parameter. Conducted across 2 XR-10 analyzers (implied internal or multi-site for the overall study context).
  • Carry-Over: High and low target concentration samples (number not specified). Conducted at three US clinical sites.
  • Comparison Studies (Whole Blood): 865 unique residual whole blood samples from pediatrics (

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The XR-Series module (XR-20) is a quantitative multi-parameter automated hematology analyzer intended for in vitro diagnostic use in screening patient populations found in clinical laboratories.

The XR-Series module classifies and enumerates the following parameters in whole blood: WBC, RBC, HGB, HCT, MCV, MCH, MCHC, PLT (PLT-I, PLT-F), NEUT%/#, LYMPH%/#, MONO%/#, EO%/#, BASO%/#, IG%/#, RDW-CV, RDW-SD, MPV, NRBC%/#, RET%/#, IPF, 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 cerebrospinal fluid (CSF), serous fluids (peritoneal, pleural) and synovial fluids. Whole blood should be collected in K2EDTA or K3EDTA anticoagulant, and serous and synovial fluids in K2EDTA anticoagulant to prevent clotting of fluid. The use of anticoagulants with CSF specimens is neither required nor recommended.

The Sysmex XR-Series module (XR-20) is a quantitative multi-parameter hematology analyzer intended to perform tests on whole blood samples collected in K2 or K3EDTA and body fluids (pleural, peritoneal and synovial) collected in K2EDTA anticoagulant. The analyzers can also perform tests on CSF, which should not be collected in any anticoagulant. The XR-Series analyzer consist of four principal units: (1) One Main Unit (XR-20) which aspirates, dilutes, mixes, and analyzes blood and body fluid samples; (2) One Auto Sampler Unit which supply samples to the Main Unit automatically; (3) IPU (Information Processing Unit) which processes data from the Main Unit and provides the operator interface with the system; (4) Pneumatic Unit which supplies pressure and vacuum from the Main Unit.

The XR-20 analyzer has an additional white progenitor cell (WPC) measuring channel and associated WPC reagents. The new WPC channel provides two separate flags for blasts and abnormal lymphocytes.

The provided FDA 510(k) Clearance Letter details the performance testing conducted for the Sysmex XR-Series (XR-20) Automated Hematology Analyzer to demonstrate its substantial equivalence to the predicate device, Sysmex XN-20. Due to the nature of the document being an FDA clearance letter summarizing performance studies rather than the full study reports, some requested details (e.g., exact sample provenance for all studies beyond "US clinical sites," specific qualifications for all experts, and the comprehensive list of acceptance criteria for all individual parameters in specific studies) are not exhaustively provided.

However, based on the information available, here's a breakdown of the acceptance criteria and the studies proving the device meets them:

Overall Acceptance Criteria & Study Design Philosophy:

The overarching acceptance criterion for this 510(k) submission is to demonstrate substantial equivalence to the predicate device, Sysmex XN-20 (K112605). This is primarily proven through:

• Analytical Performance Studies: Demonstrating that the XR-20 analyzer's performance (precision, linearity, analytical specificity, stability, limits of detection, carry-over) is "acceptable" or "met manufacturer's specifications/predefined acceptance criteria requirements."
• Method Comparison Studies: Showing a strong correlation and acceptable bias between the XR-20 and the predicate XN-20 for all claimed parameters across various patient populations and challenging samples.
• Clinical Sensitivity and Specificity Studies: For flagging capabilities, demonstrating acceptable agreement (sensitivity/specificity, PPA/NPA/OPA) with a reference method (manual microscopy) and the predicate device.

1. Table of Acceptance Criteria and Reported Device Performance

The document doesn't provide a single, consolidated table of all acceptance criteria for every parameter across all tests. Instead, it states that results "met manufacturer's specifications or predefined acceptance criteria requirements" for analytical performance tests, and provides specific correlation coefficients, slopes, intercepts, and mean differences/percent differences for method comparison studies.

Here's a partial table based on the quantifiable data presented for Method Comparison Studies (Whole Blood - Combined Sites), which is a key performance indicator for substantial equivalence. The "Acceptance Criteria" are implied by what is generally considered acceptable in hematology analyzer comparisons for FDA submissions (high correlation, small bias), and explicitly stated for certain parameters like HGB.

Implicit Acceptance Criteria (General expectation for Method Comparison based on FDA context):

• Correlation Coefficient (r): Typically > 0.95 (ideally > 0.98 or 0.99 for robust parameters)
• Slope: Close to 1.0 (ideally between 0.95 and 1.05)
• Intercept: Close to 0
• Mean Difference / % Mean Difference / Estimated Bias: Within clinically acceptable limits (often derived from biological variation or regulatory guidelines). The document explicitly mentions a bias limit for HGB: ±2% or 0.2 g/dL.

Table 1: Partial Acceptance Criteria and Reported Device Performance (Method Comparison - Whole Blood)

For other analytical performance studies (Precision, Linearity, Detection Limit, Carry-Over, Specificity, Stability), the document consistently states that the XR-20 "met manufacturer's specifications or predefined acceptance criteria requirements," supporting that specific numerical acceptance criteria were defined and achieved.

2. Sample Size and Data Provenance

• Test Set:

  • Whole Blood Method Comparison: A total of 865 unique residual whole blood samples.
  • Body Fluid Method Comparison: A total of 397 residual body fluid samples.
  • Provenance: All studies were conducted at three US clinical sites (for major studies like method comparison and reproducibility) or one internal site (for some linearity, stability, and matrix studies).
  • Retrospective/Prospective: Samples are described as "residual" (implying retrospective, de-identified leftover samples) or "prospectively collected" where specified (e.g., for some stability studies).

• Training Set: The document does not specify a training set for the algorithm, as this is a traditional in-vitro diagnostic (IVD) device (Automated Hematology Analyzer) which likely relies on fixed algorithms and established measurement principles (RF/DC Detection, Sheath Flow DC Detection, Flow Cytometry) rather than a machine learning model that requires explicit training data for its core functionality. The performance characterization is about its analytical capabilities, not about learning from a dataset to perform a task.

3. Number of Experts and Qualifications (for Ground Truth)

• Clinical Sensitivity and Specificity (Flagging Capabilities): The ground truth for flagging capabilities was established by "manual differential counts and peripheral blood smear review by experienced examiners using light microscopy (reference method) at each of the three external clinical sites." The exact number and specific qualifications (e.g., "radiologist with 10 years of experience") are not provided, but the term "experienced examiners" implies qualified personnel (e.g., clinical laboratory scientists, pathologists). Given this is a hematology analyzer, these would typically be clinical laboratory specialists or hematopathologists.

4. Adjudication Method (for the Test Set)

• Clinical Sensitivity and Specificity (Flagging): The document does not explicitly describe an adjudication method (e.g., 2+1, 3+1) for resolving discrepancies between multiple manual reviews. It states "peripheral blood smear review by experienced examiners," primarily using manual microscopy as the reference method. This implies there might be a single expert review or an internal consensus process, but no detail on conflict resolution is provided.

5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study

• No MRMC study was described. This type of study (MRMC) is typically performed for AI-assisted diagnostic tools where human reader performance is a direct outcome of interest and needs to be compared with and without AI assistance. The Sysmex XR-20 is an automated analyzer, a standalone device that performs measurements and classifications. While it outputs flags that may assist human review, its primary function isn't human-in-the-loop assistance in interpretation (like an AI for radiology image reading). Therefore, an MRMC study is not applicable for this device.

6. Standalone (Algorithm Only) Performance

• Yes, the primary performance studies are standalone algorithm/device performance. All analytical performance studies (Precision, Linearity, Detection Limit, Carry-Over, Analytical Specificity, Sample Stability) and the method comparison studies (comparing XR-20 results directly against the predicate XN-20) represent the standalone performance of the XR-20 analyzer. The device functions automatically without human input during the analysis process; therefore, human-in-the-loop performance is not directly evaluated as a primary outcome for its measurement capabilities.

7. Type of Ground Truth Used

• Analytical Ground Truth: For most analytical performance studies (Precision, Linearity, Detection Limits, Carry-Over), the "ground truth" is established by the performance of the predicate device (Sysmex XN-20) or by a well-controlled experimental setup (e.g., known dilutions for linearity, blank samples for LoB).
• Clinical Ground Truth (for flagging): For clinical sensitivity and specificity of flagging capabilities, the ground truth was expert consensus / manual review against peripheral blood smear using light microscopy. The document refers to this as the "reference method."

8. Sample Size for the Training Set

• As mentioned in point 2, no explicit training set for a machine learning algorithm is described. This device's core functionality relies on established physical and chemical principles and traditional signal processing for cell counting and classification, not a learnable AI model from a training data set in the typical sense.

9. How the Ground Truth for the Training Set Was Established

• Since there's no described "training set" for an AI/ML algorithm, this point is not applicable in the context of this traditional IVD device. The "ground truth" for verifying its performance (as detailed above) was established through comparisons to a legally marketed predicate device (XN-20) and a gold standard manual method (microscopy).

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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 XN-Series modules classify and enumerate the following parameters in whole blood: WBC, RBC, HGB, HCT, MCV, MCH, MCHC, PLT (PLT-I, PLT-F), 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 cerebrospinal fluid (CSF), serous fluids (peritoneal, pleural) and synovial fluids. Whole blood should be collected in K₂ or K₃EDTA anticoagulant and, Serous and Synovial fluids in K₂EDTA anticoagulant to prevent clotting of fluid. The use of anticoagulants with CSF specimens is neither required nor recommended.

The Sysmex® XN-Series modules (XN-10, XN-20) are multi-parameter hematology analyzers intended to perform tests on whole blood samples collected in K₂ or K₃EDTA and body fluids (pleural, peritoneal and synovial) collected in K₂ anticoagulant. It can also perform tests on CSF which should not be collected in any anticoagulant. The instrument consists of four principal units: (1) Two Main Units (XN-10, XN-20) which aspirate, dilute, mix, and analyze blood and body fluid samples; (2) Two Auto Sampler Units (SA-10, SA-20) which supply samples to the Main Unit automatically; (3) IPU (Information Processing Unit) which processes data from the Main Unit and provides the operator interface with the system; (4) Pneumatic Unit which supplies pressure and vacuum from the Main Unit. The XN-Series analyzers perform analysis using the following methods: RF/DC Detection Method, Sheath Flow DC Detection Method, and Flow Cytometry Methods using a Semiconductor Laser. Particle characterization and identification is based on detection of forward scatter, fluorescence and adaptive cluster analysis. The XN-Series analyzers automatically classify cells from whole blood and body fluids and carry out all processes automatically from aspiration of the sample to outputting the results.

The body fluid analysis mode of the XN-Series analyzers uses the 4DIFF scattergram & the RBC distribution obtained from a specialized analysis sequence to calculate & display the WBC (WBC-BF) counts, mononuclear cell (MN) / polymorphonuclear cell (PMN) counts & percentages, TC-BF (Total Count) & RBC (RBC-BF) counts found in the body fluid.

Analysis results and graphics are displayed on the IPU screen. They can be printed on any of the available printers or transmitted to a Host computer.

Here's a breakdown of the acceptance criteria and study information for the Sysmex XN-Series Automated Hematology Analyzers, based on the provided text:

1. Table of Acceptance Criteria and Reported Device Performance

The document primarily focuses on establishing substantial equivalence to a predicate device (Sysmex XE-5000) rather than explicitly stating acceptance criteria values for each parameter. Instead, it states that "Studies were performed to evaluate the equivalency of the XN-Series Automated Hematology analyzers (Modules XN-10, XN-20) to the XE-5000 Automated Hematology analyzer. Results indicated equivalent performance."

However, it does describe the types of tests performed to demonstrate performance:

2. Sample Size Used for the Test Set and Data Provenance

The document does not explicitly state the sample size used for the test set. It mentions "Studies were performed," but no specific numbers of samples are provided.

Regarding data provenance, the document does not specify the country of origin of the data or whether it was retrospective or prospective.

3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts

This information is not provided in the given text. The document refers to "manufacturer's specifications" for performance but does not detail how ground truth for the clinical performance data was established or if it involved human expert review for individual cases.

4. Adjudication Method for the Test Set

This information is not provided in the given text.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done, and the Effect Size

A Multi-Reader Multi-Case (MRMC) comparative effectiveness study was not explicitly conducted or described in the provided text. The study focused on demonstrating "equivalency" to a predicate device rather than comparing human reader performance with and without AI assistance from the device.

6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done

Yes, a standalone performance study was conducted. The document states: "Data consisting of Accuracy, Precision, Linearity and Carryover were collected to show performance to the manufacturer's specification for the Body Fluid mode." This implies a technical validation of the instrument's (algorithm's) ability to measure parameters directly, independent of human interpretation of the results beyond standard quality control.

7. The Type of Ground Truth Used

The type of ground truth used is implicit in the nature of hematology analyzers:

• For parameters like WBC, RBC, HGB, etc., the ground truth would typically be established by reference methods or calibrated controls that are considered highly accurate.
• For the body fluid mode, the "manufacturer's specifications" would define the expected accurate values against which the device's measurements (Accuracy, Precision, Linearity, Carryover) are compared. These specifications are likely derived from internal validation studies using reference methods.

8. The Sample Size for the Training Set

The document does not provide information regarding a training set. As this is an automated hematology analyzer performing quantitative measurements based on established physical and chemical principles (RF/DC Detection, Sheath Flow DC Detection, Flow Cytometry), traditional machine learning "training sets" are not typically a primary focus for regulatory submissions of this type. The device's "training" would involve the design and calibration of its internal algorithms and measuring channels.

9. How the Ground Truth for the Training Set Was Established

Since a traditional "training set" for a machine learning model is not explicitly mentioned as relevant in this context, the method for establishing its ground truth is not applicable/provided. The device's operational principles are based on known physics and established clinical measurement techniques.

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