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The Sysmex® CS-5100 is a fully automated blood coagulation analyzer intended for in vitro diagnostic use using plasma collected from venous blood samples in 3.2% sodium citrate tubes to analyze clotting, chromogenic and immunoassay methods in the clinical laboratory.

For determination of:

• Prothrombin Time (PT) seconds and PT INR with Dade® Innovin® .
• . Activated Partial Thromboplastin Time (APTT) with Dade® Actin® FSL
• . Fibrinogen (Fbg) with Dade® Thrombin Reagent
• . Coagulation Factor V with Dade® Innovin®
• . Coagulation Factor VII with Dade® Innovin®
• . Protein C with Protein C Reagent
• . Antithrombin (AT) with INNOVANCE® Antithrombin
• Protein C with Berichrom® Protein C
• D-dimer with INNOVANCE® D-Dimer

The performance of this device has not been established in neonate and pediatric patient populations.

Coagulation Factor V Deficient Plasma:
In vitro diagnostic reagent for the determination of the activity of coagulation factor V in human plasma.

Coagulation Factor II, VII and X Deficient Plasmas:
In vitro diagnostic reagents for the determination of the activity of coagulation factor II (prothrombin), coagulation factor VII and coagulation factor X in human plasma by coagulometric methods.

Protein C Reagent:
Protein C Reagent is a coagulation test for the quantitative determination of protein C activity in human plasma.

Berichrom® Protein C:
For the quantitative determination of functionally active protein C using a chromogenic substrate as an aid in the diagnosis of inherited and acquired deficiencies.

The Sysmex® CS-5100 is an automated blood coagulation instrument which can analyze samples using clotting, chromogenic and immunoassay methods. Analysis results are displayed on the Information Processing Unit (IPU) screen. They can be printed on external printers or transmitted to a host computer. Sold separately from the instrument are the associated Reagents, Controls, Calibrators, and Consumable materials. The subject of this 510(k) notification are reagent applications which perform the coagulation tests Coagulation Factor V with Dade® Innovin®, Coagulation Factor VII with Dade® Innovin®, Protein C with Protein C Reagent and Protein C with Berichrom® Protein C.

Here's an analysis of the provided text regarding the acceptance criteria and study for the Sysmex® CS-5100 device:

The document describes the performance data for the Sysmex® CS-5100 automated blood coagulation analyzer, specifically for the applications: Coagulation Factor V with Dade® Innovin®, Coagulation Factor VII with Dade® Innovin®, Protein C with Protein C Reagent, and Protein C with Berichrom® Protein C. The studies aim to demonstrate substantial equivalence to a predicate device, the Sysmex® CA-1500.

1. Table of Acceptance Criteria and Reported Device Performance

The acceptance criteria for substantial equivalence are implicitly based on demonstrating comparable performance to the predicate device. The studies aim to show that results from the new device are sufficiently similar to those from the predicate and that the new device's precision, detection capability, and linearity fall within acceptable ranges for clinical laboratory use.

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

• Method Comparison:

  • Coagulation Factor V: N = 609 total samples (133, 151, 148, 177 across 4 sites)
  • Coagulation Factor VII: N = 505 total samples (121, 145, 102, 137 across 4 sites)
  • Protein C (C Reagent): N = 624 total samples (138, 176, 110, 200 across 4 sites)
  • Protein C (Berichrom): N = 531 total samples (127, 149, 130, 125 across 4 sites)
  • Data Provenance: Four external sites in the United States. The samples were "patient samples" and seem to be prospective as they were measured on both devices in random order for comparison.

• Reproducibility Studies:

  • The sample types used for reproducibility studies are not specified as patient samples, but rather analytical samples (possibly controls or pooled plasma). The N for actual samples per run is not explicitly given, but the study design involved "two runs per day, with two replicates per run, at each of the three sites."
  • Data Provenance: Two external sites in Germany and one external site in the United States. These are prospective studies performed over 20 days.

• Detection Capability (LoQ) and Linearity Studies:

  • Sample sizes are not explicitly stated for these studies, but they involve different concentrations or dilutions to determine the limits.
  • Data Provenance: Not specified, but likely from laboratory settings where the devices were tested.

• Reference Interval Studies:

  • Coagulation Factor V, VII, Protein C (C Reagent), Protein C (Berichrom): N = 194 for each.
  • Data Provenance: Three clinical study sites in the United States. This is a prospective study of a "study population."

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

• No human "experts" established ground truth for the test set. This device is an automated in vitro diagnostic analyzer. The ground truth, in this context, is the accurately measured value of the coagulation factors and protein C using the predicate device (Sysmex® CA-1500) or established clinical analytical methods, which the new device (Sysmex® CS-5100) is compared against. Clinical laboratory standards (CLSI guidelines) are followed to ensure the validity of these reference measurements.

4. Adjudication Method

• Not applicable as this is an automated analytical device rather than a diagnostic imaging or classification system involving human interpretation. The "ground truth" or reference values are obtained through the predicate device or validated laboratory methods, not through human adjudication of ambiguous cases.

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

• No MRMC comparative effectiveness study was done. This type of study is relevant for diagnostic systems where human readers interpret output (e.g., medical images). The Sysmex® CS-5100 is an automated analyzer, and its performance is evaluated by comparing its quantitative results against a predicate device's results, not by comparing human reader performance with and without AI assistance.

6. Standalone (Algorithm Only Without Human-in-the-Loop Performance) Study

• Yes, this is a standalone study. The Sysmex® CS-5100 is an automated instrument with an algorithm (its internal measurement and calculation processes) that generates results without real-time human intervention in the measurement process itself. The performance data presented (method comparison, reproducibility, detection capability, linearity) describe the intrinsic performance of the device's analytical capabilities. While human technicians operate and maintain the device, the core measurement is "algorithm only."

7. Type of Ground Truth Used

• Predicate Device/Method comparison: For the method comparison studies, the "ground truth" for demonstrating substantial equivalence was the measurements obtained from the predicate device (Sysmex® CA-1500).
• Established analytical methods/standards: For reproducibility, detection capability, and linearity studies, the "ground truth" refers to the expected statistical performance (e.g., target CVs, expected linear range) according to CLSI guidelines and accepted laboratory practice for quantitative measurement methods.
• Reference Intervals: For reference interval studies, the "ground truth" is derived from the measurements in a healthy population to establish the normal range, as per CLSI guidelines EP28-A3c.

8. Sample Size for the Training Set

• The document does not explicitly mention a "training set" in the context of machine learning or AI algorithm development. This device is an automated analyzer, and its operational parameters and internal algorithms would typically be developed and validated by the manufacturer using extensive internal testing and calibration with known standards and samples, rather than a distinct "training set" in the AI sense. The studies described are for validation and verification of the final product.

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

• Given that a "training set" in the AI sense is not explicitly described or applicable in the provided context for this type of IVD device, this question is not directly answerable from the document. The development of such an analyzer involves engineering design, physical and chemical principles, and calibration with reference materials, rather than training an algorithm on a 'ground truth' dataset in the same way an AI for image classification would be trained.

Ask a specific question about this device

The Sysmex® CS-5100 is a fully automated blood coagulation analyzer intended for in vitro diagnostic use using plasma collected from venous blood samples in 3.2% sodium citrate tubes to analyze clotting, chromogenic and immunoassay methods in the clinical laboratory.

For determination of:

· Prothrombin Time (PT) seconds and PT INR with Dade® Innovin®

• · Activated Partial Thromboplastin Time (APTT) with Dade® Actin® FSL
  · Fibrinogen (Fbg) with Dade® Thrombin Reagent

• · Antithrombin (AT) with INNOVANCE® Antithrombin
  · D-dimer with INNOVANCE® D-Dimer.

The performance of this device has not been established in neonate and pediatic patient populations.

The Sysmex CS-5100 is an automated blood coagulation instrument which can analyze samples using clotting, chromogenic and immunoassay methods. Analysis results are displayed on the Information Processing Unit (IPU) screen. They can be printed on external printers or transmitted to a host computer. Sold separately from the instrument are the associated:

• Reagents ■
• . Controls
• 트 Calibrators
• I Consumable materials

The subject of this 510(k) notification is to expand the use of the INNOVANCE® D-Dimer for the exclusion of Deep Vein Thrombosis on Sysmex CS-5100. All other established indications, performance and technology characteristics as cleared under K150678 remain unchanged.

Acceptance Criteria and Device Performance for Sysmex CS-5100 (D-Dimer DVT Exclusion)

This document describes the acceptance criteria and study proving the Sysmex CS-5100, specifically for the INNOVANCE® D-Dimer assay's extended indication for exclusion of Deep Vein Thrombosis (DVT), meets these criteria.

1. Acceptance Criteria and Reported Device Performance

The acceptance criteria for the INNOVANCE® D-Dimer assay on the Sysmex CS-5100 for DVT exclusion are specifically defined by statistical measures of diagnostic accuracy, primarily Sensitivity, Specificity, and Negative Predictive Value (NPV), with a focus on their lower bound of the 95% confidence interval (LCL). The table below summarizes the reported device performance across different study populations. The predicate device (Sysmex CA-1500) data is included for comparison where available.

Comparison of DVT Exclusion Performance: Sysmex CS-5100 vs. Sysmex CA-1500 (Predicate)

*The predicate device's performance is listed as "The following instrument-specific sensitivity, specificity and negative predictive value (NPV) with upper and lower 95 % confidence limits (CL) were obtained with the INNOVANCE® D-Dimer clinical cutoff of 0.50 mg/L (FEU) for patients with unlikely pre-test probability." The specific wording for acceptance criteria for the new device is: "The values must be equal to or better than the predicate's performance while maintaining an equivalent confidence interval". The reported performance for the Sysmex CS-5100 matches or exceeds the predicate.

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

The DVT exclusion validation study for the Sysmex CS-5100 involved a initial prospective collection of 1907 consecutive outpatients with suspected DVT. After exclusions (including 213 patients with previously documented or chronic DVT), a total of 1317 patients were available for final analysis.

The data provenance is multicenter, prospective. The study included patients from both US and OUS (Outside US) sites:

• US sites: 803 patients
• OUS sites: 514 patients

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

The document does not explicitly state the number of experts or their specific qualifications used to establish the ground truth for the test set.

However, the ground truth was established by:

• Imaging methods (e.g., ultrasound) for patients with no or a positive D-dimer result by the study center's D-dimer assay, or at the physician's discretion for patients with a negative D-dimer.
• Three-month follow-up to evaluate potential development of DVT for all patients with a negative initial clinical diagnosis of DVT.

This implies that the ground truth was determined by clinical diagnosis using imaging results and clinical follow-up by treating physicians or specialists, rather than by independent expert reviewers of the D-Dimer results themselves.

4. Adjudication Method for the Test Set

The document does not explicitly describe an adjudication method for the test set in the traditional sense (e.g., 2+1, 3+1 expert review of independent interpretations).

The ground truth was established through a combination of:

• Imaging: Decisions based on imaging were likely made by radiologists or sonographers.
• Clinical follow-up: Clinical outcomes were assessed by physicians.

There is no mention of a formal adjudication process between multiple independent reviewers of the D-dimer results or the imaging findings.

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

There is no mention of a Multi-Reader Multi-Case (MRMC) comparative effectiveness study being conducted as part of this submission for the Sysmex CS-5100's DVT exclusion indication.

This is an in vitro diagnostic device (automated coagulation analyzer), and its performance is evaluated based on the accuracy of its quantitative D-dimer measurements and the derived diagnostic metrics (Sensitivity, Specificity, NPV) against clinical ground truth, rather than human interpretation with and without AI assistance.

6. Standalone (Algorithm Only) Performance

The study primarily evaluates the standalone performance of the INNOVANCE® D-Dimer assay on the Sysmex CS-5100. The device generates a D-dimer result, which is then interpreted by comparing it to a cut-off value (0.50 mg/L FEU) to determine a positive or negative diagnosis for DVT exclusion. This is an "algorithm only" type of performance, as it quantifies a biomarker without direct human visual interpretation of an image or signal.

7. Type of Ground Truth Used

The ground truth used was a combination of clinical outcomes data and diagnostic imaging:

• Diagnostic Imaging: "Patients with no or a positive D-dimer result with the D-dimer assay used at the respective study center were evaluated by imaging methods, e.g. ultrasound."
• Outcomes Data (Clinical Follow-up): "All patients with a negative clinical diagnosis of DVT at presentation were followed up after three months to evaluate potential development of DVT."

This establishes a robust clinical diagnosis of DVT as the ground truth.

8. Sample Size for the Training Set

The document does not provide information on a specific training set size or methodology for the INNOVANCE® D-Dimer assay on the Sysmex CS-5100 related to its DVT exclusion indication.

This submission is for an extended indication of an existing device (Sysmex CS-5100) and an existing assay (INNOVANCE® D-Dimer), which likely had its primary development and calibration (analogous to training) performed prior to this specific DVT exclusion validation study. The current study focuses on clinical validation of the assay's performance for this specific indication.

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

As noted above, the document does not describe a specific training set or how its ground truth was established for the DVT exclusion indication. The information provided pertains to the validation (test) set.

It can be inferred that earlier development work for the INNOVANCE® D-Dimer assay, possibly on previous Sysmex analyzers, involved methods similar to the current validation study to establish its accuracy for general D-dimer measurements. However, details of such "training set" establishment are not part of this 510(k) summary for the extended DVT exclusion indication.

Ask a specific question about this device

The Sysmex® CS-5100 is a fully automated blood coagulation analyzer intended for in vitro diagnostic use using plasma collected from venous blood samples in 3.2% sodium citrate tubes to analyze clotting, chromogenic and immunoassay methods in the clinical laboratory.

For determination of:

• Prothrombin Time (PT) seconds and PT INR with Dade® Innovin®
• Activated Partial Thromboplastin Time (APTT) with Dade® Actin® FSL
• Fibrinogen (Fbg) with Dade® Thrombin Reagent
• Antithrombin (AT) with INNOVANCE® Antithrombin
• D-dimer with INNOVANCE® D-Dimer

The performance of this device has not been established in neonate and pediatric patient populations.

The Sysmex CS-5100 is an automated blood coagulation instrument which can analyze samples using clotting, chromogenic and immunoassay methods. Analysis results are displayed on the Information Processing Unit (IPU) screen. They can be printed on external printers or transmitted to a host computer. Sold separately from the instrument are the associated Reagents, Controls, Calibrators, and Consumable materials. The subject of this 510(k) notification are reagent applications which perform the coagulation tests Prothrombin Time (PT) seconds and PT INR with Dade® Innovin®; Activated Partial Thromboplastin Time (APTT) with Dade® Actin® FSL; Fibrinogen (Fbg) with Dade® Thrombin Reagent; Antithrombin (AT) with INNOVANCE® Antithrombin; and D-dimer with INNOVANCE® D-Dimer.

Here's an analysis of the acceptance criteria and the studies performed for the Sysmex CS-5100 device, based on the provided document:

1. Table of Acceptance Criteria and Reported Device Performance

The document does not explicitly state pre-defined acceptance criteria values for most of the performance metrics within the tables. Instead, it states that "Results from each application met the pre-established acceptance criteria" for method comparison, and "The data for all tested reagents met the pre-determined acceptance criteria" for detection capability. For linearity, it states "All reagents met the pre-determined acceptance criteria."

However, we can infer some implied criteria based on the reported values alongside statements of acceptance, especially for Method Comparison, Reproducibility, Detection Capability, and the D-Dimer PE Exclusion Study. For the D-Dimer study, specific lower bounds for 95% LCL are provided for sensitivity and NPV, which act as de facto acceptance criteria.

Inferred Acceptance Criteria and Reported Performance for Sysmex CS-5100:

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

• Method Comparison:

  • Sample Sizes:
    • PT (seconds): n=469 (combined from 3 sites: n=125, n=209, n=135)
    • PT (INR): n=465 (combined from 3 sites: n=122, n=208, n=135)
    • APTT: n=466 (combined from 3 sites: n=126, n=210, n=130)
    • Fibrinogen: n=368 (combined from 3 sites: n=145, n=91, n=132)
    • Antithrombin: n=381 (combined from 3 sites: n=135, n=120, n=126)
    • D-dimer: n=361 (combined from 3 sites: n=137, n=108, n=116)
  • Data Provenance: Conducted at three external sites in the United States (US). The samples were patient samples.

• Reproducibility Studies:

  • Sample Sizes: Not explicitly stated as 'n=' count for each sample tested, but refers to "Sample Range (mean of all sites)" for each application. These studies involved "two runs per day, with two replicates per run, at each of the three sites". Given the "20-day precision studies", this implies a significant number of measurements for each sample type.
  • Data Provenance: Two external sites in Germany and one external site in the United States.

• Detection Capability Studies:

  • Sample Sizes: Not explicitly stated, but performed for specific reagents: Fibrinogen, Antithrombin, and D-dimer.
  • Data Provenance: Not explicitly stated, but typically in vitro studies.

• Linearity & Measuring Range Studies:

  • Sample Sizes: Not explicitly stated, but performed for Fibrinogen, Antithrombin, and D-dimer.
  • Data Provenance: Not explicitly stated, but typically in vitro studies.

• Reference Interval Studies:

  • Sample Sizes: Not explicitly stated as a number, but indicates the study population "did not include neonate and pediatric sample populations".
  • Data Provenance: Conducted at three clinical study sites in the United States.

• D-Dimer PE Exclusion Validation Study:

  • Initial Patients: 1930 consecutive outpatients.
  • Excluded Patients: 96.
  • Patients for Final Analysis: n=1467 (US: n=1424, OUS: n=43).
  • Data Provenance: Multi-center study using frozen specimens collected prospectively from outpatients presenting to emergency or ambulatory departments with suspected PE. Data from both the US and "OUS" (Outside US, specifically European population for prevalence) were included.

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

• For Method Comparison, Reproducibility, Detection Capability, Linearity, and Reference Intervals: The ground truth for these analytical performance studies is established by the methods themselves, often comparing the device to a reference method or evaluating inherent precision characteristics against statistical benchmarks. No human experts are described for establishing ground truth in these sections.

• For D-Dimer PE Exclusion Validation Study:

  • Ground Truth Establishment: The ground truth for PE diagnosis was established through imaging methods (e.g., spiral CT and/or VO scan) and 3-month follow-up for patients with initial negative diagnosis.
  • Number/Qualifications of Experts: The document mentions "physician's discretion" for imaging and that "All potentially eligible patients were evaluated using the Wells' rules...". This implies that medical professionals (e.g., emergency physicians, radiologists, other clinicians) were involved in the diagnosis and follow-up, but the specific number and detailed qualifications of these individual experts are not provided.

4. Adjudication Method for the Test Set

• For Method Comparison, Reproducibility, Detection Capability, Linearity, and Reference Intervals: No adjudication method as typically understood for human interpretation of data (e.g., 2+1 rule) is described. These are analytical performance studies where results are quantitative values compared against other instruments or statistical metrics.

• For D-Dimer PE Exclusion Validation Study: The ground truth involved a combination of imaging and 3-month follow-up. While a final diagnosis would likely involve a consensus among the treating clinicians or specialists (e.g., radiologists, internists), no explicit "adjudication method" (like multiple readers reaching a consensus on an image) is described for the final PE diagnosis. The process relies on standard clinical diagnostic pathways and follow-up.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance

• No, an MRMC comparative effectiveness study involving human readers with/without AI assistance was not done. The Sysmex CS-5100 is an automated blood coagulation analyzer, not an AI-powered diagnostic imaging tool that assists human readers. The studies focus on the analytical performance of the instrument itself and its diagnostic utility (e.g., D-dimer for PE exclusion).

6. If a standalone (i.e., algorithm only without human-in-the-loop performance) was done

• Yes, the studies described are standalone performance evaluations of the device (or algorithm if you consider the reagent-instrument combination an 'algorithm') in an automated setting. The device operates automatically, and the performance data (method comparison, reproducibility, detection capability, linearity, D-dimer PE exclusion) reflect its direct analytical output without direct human interpretation influencing the measurement itself at the point of testing. Human input is involved in sample collection, entering patient data, and clinical interpretation of the results, but not in the "reading" of the output in a way that an AI for image analysis would be 'standalone'.

7. The type of ground truth used (expert consensus, pathology, outcomes data, etc.)

• For Method Comparison: The ground truth is the result from the predicate device (Sysmex CA-1500), which is a legally marketed device for the same intended use.
• For D-Dimer PE Exclusion Validation Study: The ground truth for the presence or absence of PE was based on a combination of imaging methods (e.g., spiral CT and/or VO scan) and 3-month clinical outcomes data (follow-up) to confirm the absence of PE in initially negative cases.

8. The sample size for the training set

The document describes premarket notification for a medical device (instrument), not an AI/ML algorithm that typically requires a distinct training set for model development and a test set for performance evaluation. For this type of device, the "training" analogous to an AI model would be the internal development and calibration of the instrument by the manufacturer using their own data, which is not typically detailed in a 510(k) summary in terms of "training set sample size." The studies presented are all performance validations of the final device. Therefore, a specific "training set sample size" is not applicable/provided in this context.

9. How the ground truth for the training set was established

As there is no "training set" described in the context of an AI/ML algorithm development, this question is not applicable to this device submission. The device's internal calibration and development would have used reference materials and established laboratory methods, but these are not referred to as a "training set" with ground truth established in the same manner as for an AI model.

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